2019年10月, Support Office for Females Researchers Front office for Human Resource Education and Development, Global Networking Award 2019　　　　　　　　　　　　　　　
Global Networking Award 2019
アメングアル オルガ

1999年05月, Faculty of Medicine, Autonoma University, Madrid, Spain, Award to the best PhD of the year　　　　　　　　　　　　　　　
Best PhD Award
Olga Amengual

Phosphatidylserine-Dependent Anti-prothrombin Antibodies as a Key Predictor for Systemic Lupus Erythematosus in Patients with Primary Antiphospholipid Syndrome: A retrospective longitudinal cohort study.
Jiang Wei, Yuichiro Fujieda, Yusuke Fujita, Yusuke Ogata, Ryo Hisada, Michihito Kono, Olga Amengual, Masaru Kato, Tatsuya Atsumi
Modern rheumatology, 2024年08月27日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder characterized by thrombosis and pregnancy morbidity. Although PAPS is distinct from systemic lupus erythematosus (SLE), the two conditions share clinical features and susceptibility genes. Progression from PAPS to SLE is well-recognized. However, risk factors for this transition are poorly understood. We aimed to identify predictors of progression to SLE in patients with PAPS. METHODS: A longitudinal single-center study was conducted at Hokkaido University Hospital from 1990 to 2021. Baseline characteristics including clinical features, laboratory data, aPL profiles were compared between patients who progressed to SLE (SLE group) and those who did not (non-SLE group). RESULTS: Among 64 patients diagnosed with PAPS at baseline, nine (13.8%) progressed to SLE over a mean follow-up of 9 years (incidence rate, 1.61 per 100 person-years). At the diagnosis of PAPS, the SLE group had a higher prevalence of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-dsDNA antibodies compared to the non-SLE group. Other clinical findings, autoantibody profiles, and serum complement levels were similar between the two groups. Multivariate Cox analysis showed that IgG aPS/PT was significantly associated with SLE development (Hazard ratio: 10.3, 95% CI: 1.13-92.6, p=0.04). CONCLUSION: IgG aPS/PT may be a predictive factor for new-onset SLE in patients with PAPS, suggesting its utility in guiding risk stratification and monitoring strategies for these patients.

Relation between hydroxychloroquine dose and continuation rate in patients with systemic lupus erythematosus.
Shuhei Takeyama, Michihito Kono, Kuniyuki Aso, Kazuro Kamada, Maria Tada, Masato Tarumi, Yui Kosumi, Masaru Yoshimura, Keita Ninagawa, Ryo Hisada, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Tatsuya Atsumi
Modern rheumatology, 2024年08月06日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Hydroxychloroquine (HCQ) is recommended at a target dose of 5 mg/kg per actual body weight to reduce the risk of retinopathy in systemic lupus erythematosus (SLE). However, the efficacy of HCQ has been established at doses of 6.5 mg/kg per ideal body weight. This study aimed to clarify the effects of the HCQ dose on the continuation rate in Japanese patients, who generally have a lower body mass index than Western patients. METHODS: This retrospective single-centre observational study enrolled patients with SLE on HCQ therapy. Patients were divided into two groups with a dose per actual body weight [the low-dose (<5 mg/kg) group and the high-dose (≥5 mg/kg) group], and continuation rates were compared. The efficacy of 1-year HCQ therapy was assessed in patients without additional immunosuppressive agents and biologics. RESULTS: Of the 231 patients enrolled, 48 (20.8%) discontinued HCQ. The HCQ dose per actual body weight was identified as an independent risk factor for discontinuation. The low-dose group showed a significantly higher 1-year HCQ continuation rate than the high-dose group (83.2% vs. 72.8%, respectively). Both groups showed reductions in glucocorticoid requirement and serological activity after 1-year HCQ therapy. CONCLUSIONS: HCQ <5 mg/kg per actual body weight may facilitate greater continuation.

Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models.
Maria Tada, Yuki Kudo, Michihito Kono, Masatoshi Kanda, Shuhei Takeyama, Kodai Sakiyama, Hotaka Ishizu, Tomohiro Shimizu, Tsutomu Endo, Ryo Hisada, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Norimasa Iwasaki, Tatsuya Atsumi
Clinical immunology (Orlando, Fla.), 264, 110255, 110255, 2024年05月18日, ［国際誌］
英語, 研究論文（学術雑誌）, Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.

The chest CT signs for pulmonary veno-occlusive disease correlate with pulmonary haemodynamics in systemic sclerosis.
Haruka Moriya, Masaru Kato, Ryo Hisada, Keita Ninagawa, Maria Tada, Kodai Sakiyama, Mitsutaka Yasuda, Michihito Kono, Yuichiro Fujieda, Olga Amengual, Yasuka Kikuchi, Ichizo Tsujino, Takahiro Sato, Tatsuya Atsumi
Rheumatology (Oxford, England), 2023年09月15日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) sometimes accompanies pulmonary veno-occlusive disease (PVOD). We aimed to reveal the relation between clinical signs of PVOD and severing of pulmonary vasculopathy in SSc. METHODS: This study comprised 52 consecutive SSc patients who had pulmonary haemodynamic abnormalities (mPAP > 20 mmHg, PVR > 2 W.U. or PAWP > 15 mmHg). The chest CT scan was evaluated in all patients. Patients were divided into two groups, the 0-1 group and the 2-3 group, according to the number of chest CT signs for PVOD, including 1) mediastinal lymph node enlargement, 2) thickened interlobular septal wall, and 3) ground glass opacity. Pulmonary haemodynamics, echocardiography and MRI-based cardiac function, pulmonary function, and serum biomarkers were compared between the two groups. RESULTS: Mediastinal lymph node enlargement, thickened interlobular septal wall, and ground glass opacity were observed in 11 (21%), 32 (62%), and 11 (21%) patients, respectively. The 2-3 group (n = 15) had higher mPAP (p= 0.02) while lower DLco/VA (p= 0.02) compared with the 0-1 group (n = 37). Other parameters, including PAWP, cardiac output, left ventricular ejection fraction, left atrial diameter, forced vital capacity, brain natriuretic peptide, and Krebs von den Lunge-6 were not different between the two groups. CONCLUSION: The CT signs for PVOD had positive correlation with mPAP but negative correlation with DLco in SSc patients, indicating that PAH-SSc may reflect a spectrum of pulmonary vascular disease that ranges from the pulmonary artery to the vein.

Damage measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody-positive patients included in the APS ACTION registry
Gustavo G M Balbi, Yasaman Ahmadzadeh, Maria G Tektonidou, Vittorio Pengo, Savino Sciascia, Amaia Ugarte, H Michael Belmont, Chary Lopez-Pedrera, Paul R Fortin, Denis Wahl, Maria Gerosa, Guilherme R de Jesús, Lanlan Ji, Tatsuya Atsumi, Maria Efthymiou, D Ware Branch, Cecilia Nalli, Esther Rodriguez Almaraz, Michelle Petri, Ricard Cervera, Jason S Knight, Bahar Artim-Esen, Rohan Willis, Maria Laura Bertolaccini, Hannah Cohen, Robert Roubey, Doruk Erkan, Danieli Castro Oliveira de Andrade, JoAnn Vega, Guillermo Pons-Estel, Bill Giannakopoulos, Steve Krilis, Guilherme de Jesus, Roger Levy, Flavio Signorelli, Danieli Andrade, Gustavo Balbi, Ann E Clarke, Leslie Skeith, Paul R Fortin, Lanlan Ji, Zhouli Zhang, Chengde Yang, Hui Shi, Stephane Zuily, Denis Wahl, Maria G Tektonidou, Cecilia Nalli, Laura Andreoli, Angela Tincani, Cecilia B Chighizola, Maria Gerosa, Pierluigi Meroni, Vittorio Pengo, Chunyan Cheng, Giulia Pazzola, Savino Sciascia, Silvia Foddai, Massimo Radin, Stacy Davis, Olga Amengual, Tatsuya Atsumi, Imad Uthman, Maarten Limper, Philip de Groot, Guillermo Ruiz - Irastorza, Amaia Ugarte, Ignasi Rodriguez-Pinto, Ricard Cervera, Jose Pardos-Gea, Esther Rodriguez Almaraz, Maria Angeles Aguirre Zamorano, Chary Lopez-Pedrera, Bahar Artim-Esen, Maria Laura Bertolaccini, Hannah Cohen, Maria Efthymiou, Ian Mackie, Giovanni Sanna, Jason Knight, Yu Zuo, Michelle Petri, Rebecca K Leaf, Robert Roubey, Thomas Ortel, Rohan Willis, Nina Kello, Michael Belmont, Steven Levine, Jacob Rand, Medha Barbhaiya, Doruk Erkan, Jane Salmon, Michael Lockshin, Ali A Duarte Garcia, D Ware Branch
Rheumatology, Oxford University Press (OUP), 2023年06月12日, ［査読有り］
英語, 研究論文（学術雑誌）, Abstract

Objectives

Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients.

Methods

In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage.

Results

Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aβ2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P &lt; 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016).

Conclusions

DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study
Elena Gkrouzman, Rohan Willis, Danieli Andrade, Maria G. Tektonidou, Vittorio Pengo, Guillermo Ruiz-Irastorza, H. Michael Belmont, Paul R. Fortin, Maria Gerosa, Flavio Signorelli, Tatsuya Atsumi, D. Ware Branch, Cecilia Nalli, Esther Rodriguez-Almaraz, Michelle A. Petri, Ricard Cervera, Jason S. Knight, Maria Efthymiou, Hannah Cohen, Maria Laura Bertolaccini, Doruk Erkan, Robert Roubey, Guillermo Pons-Estel, Bill Giannakopoulos, Steve Krilis, Guilherme de Jesus, Roger Levy, Flavio Signorelli, Danieli Andrade, Gustavo Balbi, Ann E. Clarke, Leslie Skeith, Paul R. Fortin, Lanlan Ji, Zhouli Zhang, Chengde Yang, Hui Shi, Stephane Zuily, Denis Wahl, Maria G. Tektonidou, Cecilia Nalli, Laura Andreoli, Angela Tincani, Cecilia B. Chighizola, Maria Gerosa, Pierluigi Meroni, Vittorio Pengo, Chunyan Cheng, Giulia Pazzola, Savino Sciascia, Silvia Foddai, Massimo Radin, Stacy Davis, Olga Amengual, Tatsuya Atsumi, Imad Uthman, Maarten Limper, Philip de Groot, Guillermo Ruiz—Irastorza, Amaia Ugarte, Ignasi Rodriguez-Pinto, Ricard Cervera, Jose Pardos-Gea, Esther Rodriguez Almaraz, Maria Jose Cuadrado, Maria Angeles Aguirre Zamorano, Chary Lopez-Pedrera, Bahar Artim-Esen, Murat Inanc, Maria Laura Bertolaccini, Hannah Cohen, Maria Efthymiou, Munther Khamashta, Ian Mackie, Giovanni Sanna, Jason Knight, Yu Zuo, Michelle Petri, Rebecca K. Leaf, Robert Roubey, Thomas Ortel, Emilio Gonzalez, Rohan Willis, Nina Kello, Michael Belmont, Steven Levine, Jacob Rand, Medha Barbhaiya, Doruk Erkan, Jane Salmon, Michael Lockshin, Ali A. Duarte Garcia, D. Ware Branch
Laboratory Investigation, 103, 6, 100147, 100147, Elsevier BV, 2023年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Anti–Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody–Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Clinical Database and Repository
Yu Zuo, Sherwin Navaz, Alex Tsodikov, Katarina Kmetova, Lyndsay Kluge, Amala Ambati, Claire K. Hoy, Srilakshmi Yalavarthi, Danieli de Andrade, Maria G. Tektonidou, Savino Sciascia, Vittorio Pengo, Guillermo Ruiz‐Irastorza, H. Michael Belmont, Maria Gerosa, Paul R. Fortin, Guilherme Ramires de Jesus, D. Ware Branch, Laura Andreoli, Esther Rodriguez‐Almaraz, Michelle Petri, Ricard Cervera, Rohan Willis, David R. Karp, Quan‐Zhen Li, Hannah Cohen, Maria Laura Bertolaccini, Doruk Erkan, Jason S. Knight
Arthritis & Rheumatology, 75, 8, 1407, 1414, Wiley, 2023年05月18日, ［査読有り］
英語, 研究論文（学術雑誌）, Objective

This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti–neutrophil extracellular trap (anti‐NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody–positive patients who did not have lupus.

Methods

Anti‐NET IgG/IgM levels were measured in serum samples from 389 aPL‐positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform.

Results

We found elevated levels of anti‐NET IgG and/or IgM in 45% of the aPL‐positive patients. High anti‐NET antibody levels are associated with more circulating myeloperoxidase (MPO)–DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti‐NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti‐NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti‐NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti‐NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO–DNA complexes, and nucleosomes. Anti‐NET IgM positivity was associated with autoantibodies targeting single‐stranded DNA, double‐stranded DNA, and proliferating cell nuclear antigen.

Conclusion

These data reveal high levels of anti‐NET antibodies in 45% of aPL‐positive patients, where they potentially activate the complement cascade. While anti‐NET IgM may especially recognize DNA in NETs, anti‐NET IgG species appear to be more likely to target NET‐associated protein antigens.

Hypothalamic lesion in a neuropsychiatric lupus patient with narcolepsy
H Moriya, Y Fujieda, O Amengual, T Kanbayashi, T Atsumi
Scandinavian Journal of Rheumatology, 52, 4, 444, 446, Informa UK Limited, 2023年04月12日
英語, 研究論文（学術雑誌）

Fluctuation of Anti–Domain 1 and Anti–β₂‐Glycoprotein I Antibody Titers Over Time in Patients With Persistently Positive Antiphospholipid Antibodies
Cecilia B. Chighizola, Francesca Pregnolato, Danieli Andrade, Maria Tektonidou, Vittorio Pengo, Guillermo Ruiz‐Irastorza, H. Michael Belmont, Maria Gerosa, Paul Fortin, D. Ware Branch, Laura Andreoli, Michelle A. Petri, Ricard Cervera, Jason S. Knight, Rohan Willis, Maria Efthymiou, Hannah Cohen, Doruk Erkan, Maria Laura Bertolaccini
Arthritis & Rheumatology, 75, 6, 984, 995, Wiley, 2023年04月02日, ［査読有り］
英語, 研究論文（学術雑誌）, Objective

The present study was undertaken to longitudinally evaluate titers of antibodies against β₂‐glycoprotein I (anti‐β₂GPI) and domain 1 (anti‐D1), to identify predictors of variations in anti‐β₂GPI and anti‐D1 titers, and to clarify whether antibody titer fluctuations predict thrombosis in a large international cohort of patients who were persistently positive for antiphospholipid antibodies (aPL) in the APS ACTION Registry.

Methods

Patients with available blood samples from at least 4 time points (at baseline [year 1] and at years 2–4 of follow‐up) were included. Detection of anti‐β₂GPI and anti‐D1 IgG antibodies was performed using chemiluminescence (BIO‐FLASH; INOVA Diagnostics).

Results

Among 230 patients in the study cohort, anti‐D1 and anti‐β₂GPI titers decreased significantly over time (P < 0.0001 and P = 0.010, respectively). After adjustment for age, sex, and number of positive aPL tests, we found that the fluctuations in anti‐D1 and anti‐β₂GPI titer levels were associated with treatment with hydroxychloroquine (HCQ) at each time point. Treatment with HCQ, but not immunosuppressive agents, was associated with 1.3‐fold and 1.4‐fold decreases in anti‐D1 and anti‐β₂GPI titers, respectively. Incident vascular events were associated with 1.9‐fold and 2.1‐fold increases in anti‐D1 and anti‐β₂GPI titers, respectively. Anti‐D1 and anti‐β₂GPI titers at the time of thrombosis were lower compared to titers at other time points. A 1.6‐fold decrease in anti‐D1 titers and a 2‐fold decrease in anti‐β₂GPI titers conferred odds ratios for incident thrombosis of 6.0 (95% confidence interval [95% CI] 0.62–59.3) and 9.4 (95% CI 1.1–80.2), respectively.

Conclusion

Treatment with HCQ and incident vascular events in aPL‐positive patients predicted significant anti‐D1 and anti‐β₂GPI titer fluctuations over time. Both anti‐D1 and anti‐β₂GPI titers decreased around the time of thrombosis, with potential clinical relevance.

Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming
Kuniyuki Aso, Michihito Kono, Masatoshi Kanda, Yuki Kudo, Kodai Sakiyama, Ryo Hisada, Kohei Karino, Yusho Ueda, Daigo Nakazawa, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Tatsuya Atsumi
Nature Communications, 14, 1, Springer Science and Business Media LLC, 2023年02月27日, ［査読有り］
研究論文（学術雑誌）, Abstract

Dysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell differentiation by orchestrating metabolic and epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis and oxidative phosphorylation in Th17- and Treg-polarizing T cells. Following treatment with itaconate, the S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels are decreased by inhibiting the synthetic enzyme activities in Th17 and Treg cells, respectively. Consequently, these metabolic changes are associated with altered chromatin accessibility of essential transcription factors and key gene expression in Th17 and Treg cell differentiation, including decreased RORγt binding at the Il17a promoter. The adoptive transfer of itaconate-treated Th17-polarizing T cells ameliorates experimental autoimmune encephalomyelitis. These results indicate that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and could be a potential therapeutic agent for autoimmune diseases.

Disease activity at conception predicts lupus flare up to two years after birth: A multicentre long term follow-up study.
Massimo Radin, Karen Schreiber, Irene Cecchi, Flavio Signorelli, Guilherme de Jesús, Kuniyuki Aso, Michihito Kono, Maria Letizia Urban, Beatrice Bacco, Silvia Gallo Cassarino, Luca Lo Sardo, Silvia Grazietta Foddai, Alice Barinotti, Ignacio Gómez-García, María Isabel Quaglia, Yohana Tissera, Fiammetta Gervasoni, María Ángeles Aguirre-Zamorano, Paula Alba, Chiara Benedetto, Tatsuya Atsumi, Olga Amengual, Giacomo Emmi, Danieli Andrade, Luca Marozio, Dario Roccatello, Savino Sciascia
Seminars in arthritis and rheumatism, 57, 152113, 152113, 2022年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To assess predicting factors that might influence systemic lupus erythematosus (SLE) disease activity in women in an extended follow-up period of two years after giving birth with clinical assessments every three months. METHODS: The study was design as an international retrospective study, enrolling 119 women with a first birth and with a two years follow-up. RESULTS: Joint involvement was present in 80% of patients, acute cutaneous in 64%, haematological in 54%, renal in 41% and 75% of patients were positive for anti-dsDNA. The mean SLE disease activity index 2000 (SLEDAI-2K) at diagnosis was 13.5±6.8 and at first birth was 2.8±4.4. At follow-up, 51.3% of patients had at least one flare after a mean time after birth of 9±6.3 months (mean flare per patient 0.94±1.1). The most frequent flare manifestations were joint involvement (48%), renal (33%), cutaneous (28%) and haematologic (20%). Patients with remission of disease (SLEDAI-2K=0; no clinical or laboratory manifestations of SLE) at conception had significantly lower rates of flares (18/49-37% vs. 43/70-61%; p=0.008). Patients who experienced a flare during pregnancy (17 patients) had higher rates of flares during follow-up (76% vs. 47%; p=0.019), lower time for first flare (4.4±2.3 months vs. 10.3±6.5; p<0.001), lower rate of remission of disease at conception (12% vs. 46%; p<0.001), lower rates of SLEDAI-2K at conception (5.9±5.6 vs. 2.3±4; p<0.001) and lower rates of exclusive breastfeeding (24% vs. 57%: p=0.009). Results were confirmed after performing multivariate analysis. CONCLUSION: Remission at conception can influence SLE disease positively, even at long-term. Planned pregnancy counseling is fundamental when managing SLE patients.

Inhibitor of nuclear factor kappa-B kinase epsilon contributes to neuropsychiatric manifestations in lupus-prone mice through microglial activation.
Kohei Karino, Michihito Kono, Shuhei Takeyama, Yuki Kudo, Masatoshi Kanda, Nobuya Abe, Kuniyuki Aso, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Olga Amengual, Tatsuya Atsumi
Arthritis & rheumatology (Hoboken, N.J.), 75, 3, 411, 423, 2022年09月13日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multi-organ dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30~40% of lupus patients and is the most severe presentation of SLE, frequently resulting in limitation of daily life. Recent studies have shown that microglia, tissue-resident macrophages in the central nervous system, are involved in the pathogenesis of NPSLE. Herein, we explored new therapeutic targets for NPSLE focusing on microglia. METHODS: RNA sequencing of microglia in MRL/lpr, lupus-prone mice, as well as that of microglia cultured in vitro with cytokines were performed. A candidate gene, which could be a therapeutic target for NPSLE, was identified and its role on microglial activation and phagocytosis was investigated using specific inhibitors and siRNA. The effect of intracerebroventricular administration of the inhibitor on the behavioral abnormalities of MRL/lpr was also evaluated. RESULTS: Transcriptome analysis revealed the upregulation of Ikbke, which encodes the inhibitor of nuclear factor kappa-B kinase epsilon (IKBKE) in both microglia from MRL/lpr mice and cytokine-stimulated microglia in vitro. Intracerebroventricular administration of an IKBKE inhibitor ameliorated cognitive function and suppressed microglial activation in MRL/lpr mice. Mechanistically, IKBKE inhibition reduced glycolysis, which dampened microglial activation and phagocytosis. CONCLUSIONS: These findings suggest that IKBKE plays a vital role in the pathogenesis of NPSLE via microglial activation, and it could serve as a therapeutic target for NPSLE.

Pathogenic neuropsychiatric effect of stress-induced microglial interleukin 12/23 axis in systemic lupus erythematosus.
Nobuya Abe, Masato Tarumi, Yuichiro Fujieda, Nobuhiko Takahashi, Kohei Karino, Mona Uchida, Michihito Kono, Yuki Tanaka, Rie Hasebe, Masaru Kato, Olga Amengual, Yoshiyuki Arinuma, Kenji Oku, Wakiro Sato, Khin Khin Tha, Miwako Yamasaki, Masahiko Watanabe, Tatsuya Atsumi, Masaaki Murakami
Annals of the rheumatic diseases, 81, 11, 1564, 1575, 2022年07月11日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The central nervous system disorder in systemic lupus erythematosus (SLE), called neuropsychiatric lupus (NPSLE), is one of the most severe phenotypes with various clinical symptoms, including mood disorder, psychosis and delirium as diffuse neuropsychological manifestations (dNPSLE). Although stress is one of the aggravating factors for neuropsychiatric symptoms, its role in the pathogenesis of dNPSLE remains to be elucidated. We aimed to investigate stress effects on the neuropsychiatric pathophysiology in SLE using lupus-prone mice and patients' data. METHODS: Sleep disturbance stress (SDS) for 2 weeks was placed on 6-8-week-old female MRL/lpr and control mice. Behavioural phenotyping, histopathological analyses and gene and protein expression analyses were performed to assess SDS-induced neuroimmunological alterations. We also evaluated cytokines of the cerebrospinal fluid and brain regional volumes in patients with dNPSLE and patients with non-dNPSLE. RESULTS: SDS-subjected MRL/lpr mice exhibited less anxiety-like behaviour, whereas stressed control mice showed increased anxiety. Furthermore, stress strongly activated the medial prefrontal cortex (mPFC) in SDS-subjected MRL/lpr. A transcriptome analysis of the PFC revealed the upregulation of microglial activation-related genes, including Il12b. We confirmed that stress-induced microglial activation and the upregulation of interleukin (IL) 12/23p40 proteins and increased dendritic spines in the mPFC of stressed MRL/lpr mice. IL-12/23p40 neutralisation and tyrosine kinase 2 inhibition mitigated the stress-induced neuropsychiatric phenotypes of MRL/lpr mice. We also found a higher level of cerebrospinal fluid IL-12/23p40 and more atrophy in the mPFC of patients with dNPSLE than those with non-dNPSLE. CONCLUSIONS: The microglial IL-12/23 axis in the mPFC might be associated with the pathogenesis and a promising therapeutic target for dNPSLE.

Pregnancy outcomes in antiphospholipid antibody positive patients: prospective results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ('Registry').　　　　　　　　　　　　　　　
Erton ZB, Sevim E, de Jesús GR, Cervera R, Ji L, Pengo V, Ugarte A, Andrade D, Andreoli L, Atsumi T, Fortin PR, Gerosa M, Zuo Y, Petri M, Sciascia S, Tektonidou MG, Aguirre-Zamorano MA, Branch DW, Erkan D, APS ACTION
Lupus Sci Med., 9, 1, e000633, 2022年06月, ［査読有り］
研究論文（学術雑誌）

Disease activity as a risk factor for venous thromboembolism in rheumatoid arthritis analysed using time-averaged DAS28CRP: a nested case-control study.
Masaru Yoshimura, Yuichiro Fujieda, Masanari Sugawara, Michihito Kono, Masaru Kato, Isao Yokota, Olga Amengual, Yoichi M Ito, Tatsuya Atsumi
Rheumatology international, 42, 11, 1939, 1946, 2022年04月06日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The objective of this study is to clarify the clinical features and risk factors of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA). We retrospectively reviewed the prevalence of VTE in RA patients who visited Hokkaido University Hospital from 2010 to 2019 and had more than 2 years of follow-up. To explore the risk to develop VTE, we selected 260 RA patients without VTE (non-VTE) via density sampling and identified the risk factors for VTE by multivariate logistic regression analysis. Univariate conditional logistic regression analysis showed older age (p < 0.0001, Odds Ratio [OR] 1.08, 95% Confidence Interval [CI] 1.04-1.14), increase of the body mass index (BMI) (p = 0.001, OR 1.17, 95% CI 1.06-1.31), higher prevalence of RA-associated lung disease (p = 0.002, OR 2.10, 95% CI 1.33-3.30) and more frequent glucocorticoid usage (p = 0.001, OR 2.09, 95% CI 1.34-3.51) in RA patients was associated with the development of VTE significantly. Furthermore, patients with higher time-averaged disease activity score 28 (DAS28) CRP were at elevated risk (p < 0.0001, OR 3.25, 95% CI 1.94-6.12). In conditional multivariate logistic regression analysis, time averaged DAS28CRP was significantly associated with the development of VTE (p = 0.0001, adjusted OR 3.40, 95% CI 1.77-7.85). Disease activity was identified as a major risk factor of VTE in patients with RA, suggesting that sustained clinical remission could be beneficial for decrease the risk of VTE.

Aberrant functional connectivity between anterior cingulate cortex and left insula in association with therapeutic response to biologics in inflammatory arthritis.
Nobuya Abe, Yuichiro Fujieda, Khin K Tha, Hisashi Narita, Kuniyuki Aso, Kohei Karino, Masatoshi Kanda, Michihito Kono, Masaru Kato, Olga Amengual, Tatsuya Atsumi
Seminars in arthritis and rheumatism, 55, 151994, 151994, 2022年03月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Brain activity is reported to be associated with individual pain susceptibility and inflammatory status, possibly contributing to disease activity assessment in inflammatory arthritis (IA) including rheumatoid arthritis (RA) and spondyloarthritis (SpA). However, what alteration of brain function associated with disease activity and therapeutic effectiveness in IA remains unclear. We aimed to identify the alterations of brain functional connectivity (FC) shared in both RA and SpA, and evaluate its relationship to anti-rheumatic treatment response using functional magnetic resonance imaging (MRI). PATIENTS AND METHODS: Structural and resting-state functional MRI data were acquired from patients with IA, patients with osteoarthritis (OA) and heathy controls (HCs). Two datasets were adopted to derive (51 IA, 56 OA, and 17 HCs) and validate (31 IA) the observations. 33 IA patients in the derivation dataset and all the patients in validation dataset required biological treatment and were clinically evaluated before and after therapy. Via whole-brain pair-wise FC analyses, we analyzed IA-specific FC measures relevant to therapeutic response to biologics. RESULTS: The value of FC between left insular cortex (IC) and anterior cingulate cortex (ACC) was significantly low in IA patients compared with OA patients and HCs. We demonstrated that the FC between left anterior long insular gyrus as a subdivision of IC and ACC was significantly associated with therapeutic response to biologics regarding the improvement of patients' global assessment (PGA) in both derivation and validation datasets. CONCLUSION: Disease-specific resting-state FC provides a means to assess the therapeutic improvement of PGA and would be a clinical decision-making tool with predictability for treatment response in both RA and SpA.

Prediction of the intolerance or non-responder to Janus kinase inhibitors in patients with rheumatoid arthritis: a preliminary retrospective study with integrative cluster analysis.
Masanari Sugawara, Yuichiro Fujieda, Atsushi Noguchi, Shun Tanimura, Yuka Shimizu, Ikuma Nakagawa, Masaru Yoshimura, Nobuya Abe, Michihito Kono, Masaru Kato, Kenji Oku, Olga Amengual, Isao Yokota, Hiroki Takahashi, Tatsuya Atsumi
Clinical and experimental rheumatology, 2021年11月03日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To identify the subpopulation of rheumatoid arthritis (RA) non-responders to Janus kinase inhibitors (JAKis) using cluster analysis. METHODS: This retrospective study enrolled RA patients who had been treated with JAKis (tofacitinib or baricitinib) between July 2013 and September 2019 in six centres. The endpoint was set as inadequate response to JAKis (JAKis-IR), defined as either non-response to JAKis or their intolerance. Non-response to JAKis was defined as achieving neither American College of Rheumatology 20% response nor Disease Activity Score (ΔDAS28-CRP) >1.2 at 12 weeks. Withdrawal time point included earlier than after 12 weeks from baseline. A hierarchical cluster analysis was performed with variables related with clinical and serological parameters at baseline. RESULTS: The 132 RA patients enrolled were classified into four groups (Group A-D). Groups consisted of three components defined at baseline, as seropositivity, advanced joint destruction, interstitial lung disease presumably associated with RA (RA-ILD). Group A (n=32): seronegative, presence of advanced joint destruction, absence of RA-ILD. Group B (n=35): seropositive, absence of advanced joint destruction and RA-ILD. Group C (n=20): seropositive, absence of advanced joint destruction, presence of RA-ILD. Group D (n=45): seropositive, presence of advanced joint destruction and RA-ILD. The rate of JAKis-IR in four groups was as follows: A, 34.3%; B, 17.1%; C, 20.0%; and D, 8.9%. The difference in JAKis-IR rate between group A and D was statistically significant. CONCLUSIONS: A subpopulation of RA patients with a combination of the following three components, seronegativity, advanced joint destruction and absence of RA-ILD, was identified as being prone to JAKis-IR.

Antiphospholipid Antibody Profile StabilitOver Time: Prospective Results From the APS ACTION Clinical Database and Repository
Gkrouzman E, Sevim E, Finik J, Andrade D, Pengo V, Sciascia S, Tektonidou MG, Ugarte A, Chighizola CB, Belmont HM, Lopez-Pedrera C, Ji L, Fortin P, Efthymiou M, de Jesus GR, Branch DW, Nalli C, Petri M, Rodriguez E, Cervera R, Knight JS, Atsumi T, Willis R, Bertolaccini ML, Cohen H, Rand J, Erkan D, APS ACTION
J Rheumatol, 48, 4, 541, 547, Journal of Rheumatology, 2021年04月, ［査読有り］
英語, Objective. The APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine (1) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and (2) predictors of unstable aPL profiles over time. Methods. A clinically meaningful aPL profile was defined as positive lupus anticoagulant (LAC) test and/or anticardiolipin (aCL)/anti-β2 glycoprotein-I (anti–β2-GPI) IgG/M ≥ 40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis. Results. Of 472 patients with clinically meaningful aPL profile at baseline (median follow-up 5.1 yrs), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable, and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate (P = 0.906) and multivariable analysis (P = 0.790). Baseline triple aPL positivity decreased (OR 0.25, 95% CI 0.10–0.64, P = 0.004) and isolated LAC test positivity increased (OR 3.3, 95% CI 1.53–7.13, P = 0.002) the odds of an unstable aPL profile over time. Conclusion. Approximately 80% of our international cohort patients with clinically meaningful aPL profiles at baseline remain stable at a median follow-up of 5 years
triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.

New insights into the pathogenic mechanisms and treatment of arterial thrombosis in antiphospholipid syndrome.
Yuichiro Fujieda, Olga Amengual
European journal of rheumatology, 2020年11月19日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Antiphospholipid syndrome (APS) is a systemic disorder clinically characterized by widespread thrombosis and obstetric complications associated with the persistent presence of antiphospholipid antibodies (aPLs). The persistent presence of aPLs represents a thrombotic risk in APS, which can be stratified according to the aPL profile. Thrombosis occurs in both arteries and veins. Notably, arterial thromboses have a higher recurrence compared with venous thromboses and a tendency for recurrence in the same vascular (arterial) site. Secondary prevention of arterial thrombosis requires more intensive treatment than prevention of venous thrombosis. Data from randomized clinical trials indicated that factor Xa inhibitors should not be recommended for APS. Recurrent thromboses in patients with APS treated with factor Xa inhibitors were mainly arterial, with a high rate of stroke. Dual antiplatelet therapy may have some benefit for preventing the recurrence of arterial thrombosis in patients with APS. This review article describes pathogenic mechanisms, clinical features, risk assessment, and management of arterial thrombosis in patients with APS. Particularly, we discuss how secondary prophylaxis may be a useful approach to reduce the occurrence of arterial thrombosis.

COVID-19 pandemic in Japan.
Olga Amengual, Tatsuya Atsumi
Rheumatology international, 2020年11月17日, ［査読有り］, ［招待有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Coronavirus Disease-2019 (COVID-19), is a global emergency. The first case of COVID-19 was confirmed in Japan in January 2020, a second outbreak of infection occurred in mid-March and a third peak at the beginning of August. The COVID-19 phenotype was milder in Japan than in other countries, although the restrictive measures applied in the country have not been as strict as in other places. Factors related to a possible reduced susceptibility to the pulmonary manifestations of SARS-CoV-2 may have contributed to better outcomes and lower mortality in Japan.

Morbidity and mortality in antiphospholipid syndrome based on cluster analysis：a 10-year longitudinal cohort study
Ogata Y, Fujieda Y, Sugawara M, Sato T, Ohnishi N, Kono Michihito, Kato M, Oku K, Amengual O, Atsumi T
22th Asia Pacific League of Associations for Rheumatology Congress, Kyoto, Japan, 60, 3, 1331, 1337, 2020年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Using cluster analysis, to identify the subgroup of patients with APS with the poorest prognosis and clarify the characteristics of that subgroup. METHODS: This is a longitudinal retrospective cohort study of APS patients. Using clinical data and the profile of aPL, cluster analysis was performed to classify the patients into subgroups. Events were defined as thrombosis, severe bleeding, and mortality. RESULTS: A total of 168 patients with APS were included. Cluster analysis classified the patients into three subgroups; Cluster A (n = 61): secondary APS, Cluster B (n = 56): accumulation of cardiovascular risks and arterial thrombosis, Cluster C (n = 61): triple positivity of aPL and venous thrombosis. Cluster B showed significantly higher frequency of the events and higher mortality compared with the other clusters (P = 0.0112 for B vs A and P = 0.0471 for B vs C). CONCLUSION: Using cluster analysis, we clarified the characteristics of the APS patients with the poorest prognosis. Risk factors for cardiovascular disease may further increase events in patients with APS.

Protective Role of Optineurin Against Joint Destruction in Rheumatoid Arthritis Synovial Fibroblasts.
Wen Shi Lee, Masaru Kato, Eri Sugawara, Michihiro Kono, Yuki Kudo, Michihito Kono, Yuichiro Fujieda, Toshiyuki Bohgaki, Olga Amengual, Kenji Oku, Shinsuke Yasuda, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi
Arthritis & rheumatology (Hoboken, N.J.), 72, 9, 1493, 1504, 2020年09月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Optineurin (OPTN) is an autophagy adaptor/receptor that acts as an intrinsic negative regulator of osteoclast differentiation. RANKL expressed by rheumatoid arthritis synovial fibroblasts (RASFs) is primarily responsible for the development of bone erosions in patients with RA. The aim of the present study was to explore the role of OPTN in the pathogenesis of joint destruction in RA. METHODS: RASFs were left untreated or incubated with tumor necrosis factor (TNF) or interferon-γ (IFNγ), and expression of OPTN by RASFs was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Expression of RANKL and osteoprotegerin (OPG) was evaluated in cultures of OPTN-reduced RASFs with or without TNF or IFNγ treatment. OPTN-reduced RASFs were cocultured with monocytes and stained for tartrate-resistant acid phosphatase (TRAP). IκBα, NF-κB1, and RelA protein levels were measured to evaluate NF-κB signaling. Expression of messenger RNA (mRNA) for matrix metalloproteinase 3 (MMP3), interleukin-6 (IL6), GATA binding protein 3 (GATA3), carbohydrate sulfotransferase 15 (CHST15), hyaluronan synthase 1 (HAS1), and GATA1 was analyzed by RT-qPCR. RESULTS: In RASFs incubated with TNF or IFNγ, OPTN expression was up-regulated and RANKL expression was increased, and these effects were further pronounced in OPTN-reduced RASFs (all P < 0.05 versus controls). OPG mRNA levels remained unchanged. Monocytes cocultured with OPTN-reduced RASFs differentiated to a greater extent into TRAP+ multinucleated cells compared to monocytes cocultured with control RASFs (P < 0.05). IκBα degradation and nuclear NF-κB1 expression following TNF treatment were both prolonged in OPTN-reduced RASFs (each P < 0.05 versus controls). MMP3 mRNA levels were up-regulated, while GATA3, CHST15, and HAS1 mRNA levels were down-regulated in OPTN-reduced RASFs (each P < 0.05 versus controls). CONCLUSION: OPTN plays a protective role in RA when it is up-regulated in RASFs in the presence of proinflammatory cytokines. Absence of OPTN might worsen RA by generating a joint-destructive state, as indicated by evidence of increased RANKL expression on RASFs and subsequent osteoclast differentiation.

Low C4 as a risk factor for severe neuropsychiatric flare in patients with systemic lupus erythematosus.
Kuniyuki Aso, Michihito Kono, Michihiro Kono, Toshiyuki Watanabe, Yuka Shimizu, Yusuke Ogata, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Olga Amengual, Shinsuke Yasuda, Tatsuya Atsumi
Lupus, 29, 10, 1238, 1247, 2020年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: This study aimed to explore the risk factors for 'severe' neuropsychiatric (NP) flare in patients with systemic lupus erythematosus (SLE). METHODS: This retrospective study comprised newly diagnosed 184 adult SLE patients who visited Hokkaido University Hospital between 2006 and 2017. In this study, severe NP flare was defined as the occurrence of at least one newly developed British Isles Lupus Assessment Group A score in the neurological domain. Overall severe NP flare-free survival was estimated by Kaplan-Meier analysis. Clinical and demographic profiles at SLE diagnosis were assessed as potential risk items in the adjusted multivariate Cox regression model. RESULTS: The median follow-up period was 7.9 years (interquartile range (IQR) 4.6-12.3) years. A total of 28 (15.2%) patients had one or more severe NP flares during the observation period. The median time from patient enrolment date to severe NP flare occurrence was 3.1 years (IQR 0.9-6.3 year). The 2- and 10-year severe NP flare-free survival rates were 92.7% and 86.0%, respectively. Among the manifestations of severe NP flare, psychosis was the most frequent (19.1%). In the multivariate model, low serum levels of C4 (hazard ratio (HR) = 3.67, p = 0.013) and severe NP manifestations at SLE diagnosis (HR = 7.11, p < 0.001) emerged as independent risk factors for developing severe NP flare. CONCLUSION: The first severe NP flare presented early in the course of SLE. Low C4 level and severe NP manifestations at SLE diagnosis could predict the development of severe NP flare.

Myofascia-dominant involvement on whole-body MRI as a risk factor for rapidly progressive interstitial lung disease in dermatomyositis.
Kohei Karino, Michihiro Kono, Michihito Kono, Keita Sakamoto, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Kenji Oku, Shinsuke Yasuda, Tatsuya Atsumi
Rheumatology (Oxford, England), 59, 7, 1734, 1742, 2020年07月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with DM. Although clinically amyopathic DM (CADM) represents risk for RPILD, the incidence rate of RPILD in patients with CADM varies widely. Whole-body (WB) MRI can reveal involvement of systemic muscle and myofascia. The objective of this study was to explore the risk factors for RPILD in patients with DM using WB-MRI. METHODS: This retrospective study comprised 41 patients with DM who underwent WB-MRI before the initiation of treatment in our hospital. Muscular and myofascial signals were scored on 42 muscular groups. The myofascia/muscle ratio was calculated and used to define the relevance of myofascia-dominant involvement. RPILD was defined as worsening of dyspnoea, hypoxaemia and radiographic ILD/fibrosis within 3 months from the onset of respiratory symptoms. RESULTS: Among the 41 patients, 17 had CADM and 30 had ILD, including 10 patients with RPILD. All patients including those with CADM showed abnormal signal intensity in both muscle and myofascia (median score: 15 and 23, respectively). Muscle signal scores positively correlated with the serum creatine kinase level (r = 0.714; P< 0.001). Patients with RPILD showed a significantly higher myofascia/muscle ratio than those without RPILD (1.929 vs 1.200; P= 0.027). Logistic regression analysis identified higher myofascia/muscle ratio as independent risk factors for developing RPILD. CONCLUSION: Myofascia-dominant involvement was defined and appreciated in patients with DM using WB-MRI. This may be one of the risk factors for RPILD.

Incidence and risk of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) after tooth extraction in patients with autoimmune disease.
Yuichiro Fujieda, Mototsugu Doi, Takuya Asaka, Masahiro Ota, Ryo Hisada, Naoki Ohnishi, Michihiro Kono, Hiraku Kameda, Daigo Nakazawa, Masaru Kato, Olga Amengual, Masahiko Takahata, Shinsuke Yasuda, Yoshimasa Kitagawa, Tatsuya Atsumi
Journal of bone and mineral metabolism, 38, 4, 581, 588, 2020年07月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a rare but serious complication in patients receiving antiresorprtive agents (AR). However, the incidence of ARONJ after tooth extraction in patients with autoimmune disease (AID) remains unclear. The present study aimed to clarify the high-risk population of ARONJ in patients with AID. MATERIALS AND METHODS: The study population comprised 232 patients treated with AR, AID or non-AID, who had undergone dental extraction from January 2011 to September 2017. The incidence and risk factors of ARONJ were analysed retrospectively. Additionally, the relationship between ARONJ and osteoporotic fracture (OF) and AR discontinuation during dental procedures was investigated. RESULTS: Of 232 patients, 10 developed ARONJ within 1 year of dental extraction. The incidence of ARONJ in patients with AID was higher than that in non-AID patients (2.0/100 person-year vs 0.5/100 person-year; p = 0.03). Among the AID patients, RA patients had strikingly high incidence of ARONJ (3.6/100 person-year). The incidence of neither ARONJ nor OF significantly differed between patients who continued and discontinued AR in the perioperative period. CONCLUSION: Patients with AID who undergo dental extraction are at high risk of ARONJ. Discontinuation of AR would not significantly contribute to reduce the incidence of ARONJ in those patients.

オートファジーは滑膜線維芽細胞におけるVIM(ビメンチン)のシトルリン化を促進し,主要組織適合性複合体クラスIIとのその相互作用を促進する【JST・京大機械翻訳】
Sugawara Eri, Kato Masaru, Kudo Yuki, Lee Wenshi, Hisada Ryo, Fujieda Yuichiro, Oku Kenji, Bohgaki Toshiyuki, Amengual Olga, Yasuda Shinsuke, Onodera Tomohiro, Hatakeyama Shigetsugu, Atsumi Tatsuya
Autophagy, 16, 5, 946, 955, 2020年05月, ［査読有り］, ［国際誌］
英語, We aimed to investigate the involvement of macroautophagy/autophagy in autoimmunity in rheumatoid arthritis (RA) through citrullination of VIM (vimentin) and its interaction with MHC class II in synovial fibroblasts (SFs). The cell surface expression of MHC class II and B7 costimulatory molecules on SFs was analyzed by flow cytometry after treatment with IFNG/IFN-γ (interferon gamma). Intracellular citrullinated autoantigens in SFs were analyzed by immunoblotting using serum from anti-citrullinated peptide antibodies (ACPA)-positive patient as a primary antibody. SFs were incubated in serum-free medium or treated with proteasome inhibitor MG132 to induce autophagy. An autophagy inhibitor 3-methyladenin (3-MA) was used. Intracellular citrullinated VIM (cVIM) was evaluated by immunoblotting and immunocytochemistry. The interaction between MHC class II and cVIM was evaluated with co-immunoprecipitation and proximity ligation assay (PLA). We demonstrated that MHC class II, CD274/B7-H1 and PDCD1LG2/B7-DC were expressed on SFs following treatment with IFNG whereas CD276/B7-H3 was detected on SFs regardless of the presence of IFNG. ACPA-positive sera recognized a 54 kDa protein in SFs. By immunoprecipitation, the 54 kDa protein recognized by RA sera was revealed to be cVIM. Following induction of autophagy, intracellular cVIM was increased in SFs but the effect was canceled by 3-MA. The interaction between MHC class II and cVIM was demonstrated by co-immunoprecipitation. Furthermore, PLA revealed the significant increase of MHC class II-cVIM interaction following induction of autophagy. Our findings suggest that SFs may contribute to the autoimmunity in RA through citrullination of VIM and its interaction with MHC class II promoted by autophagy.Abbreviations: 3-MA: 3-methyladenine; ACPA: anti-citrullinated peptide antibodies; anti-CCP: anti-cyclic citrullinated peptide antibody; cVIM: citrullinated VIM; BECN1: beclin1; DAPI: 4',6-diamidino-2-phenylindole; FBS: fetal bovine serum; HLA: human leukocyte antigen; IFNG/IFN-γ: interferon gamma; IL6: interleukin 6; IP: immunoprecipitation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFI: mean fluorescence index; MHC: major histocompatibility complex; OA: osteoarthritis; PADI: peptidyl arginine deiminase; PepA: pepstatin A; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; RA: rheumatoid arthritis; SFs: synovial fibroblasts; siRNA: small interfering RNA; VIM: vimentin.

Recommendations of the Spanish Rheumatology Society for Primary Antiphospholipid Syndrome. Part II: Obstetric Antiphospholipid Syndrome and Special Situations.　　　　　　　　　　　　　　　
アメングアル オルガ
Reumatol Clin (Engl Ed), 16, 2, 133, 148, 2020年03月, ［査読有り］, ［招待有り］
スペイン語

Recommendations of the Spanish Rheumatology Society for Primary Antiphospholipid Syndrome. Part I: Diagnosis, Evaluation and Treatment.　　　　　　　　　　　　　　　
Cáliz Cáliz R, Díaz Del Campo, Fontecha P, Galindo Izquierdo M, López Longo FJ, Martínez Zamora MÁ, Santamaria Ortiz A, Amengual Pliego O, Cuadrado Lozano MJ, Delgado Beltrán MP, Ortells LC, Pérez ECC, Rego GD, Corral SG, Varela CF, López MM, Nishishinya B, Navarro MN, Testa CP, Pérez HS, Silva-Fernández L, Taboada VMM
Reumatol Clin (Engl Ed), 16, 2, 71, 86, 2020年03月, ［査読有り］, ［招待有り］
スペイン語

B cells targeting therapy in the management of systemic lupus erythematosus.
Wen Shi Lee, Olga Amengual
Immunological medicine, 43, 1, 16, 35, 2020年03月, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which affects the majority of organs and systems. Traditional therapies do not lead to complete remission of disease but only relieve symptoms and inflammation. B cells are the most important effector cell types in the pathogenesis of SLE. Therefore, therapies targeting B cells and their related cytokines are a very important milestone for SLE treatment. Several biologics that modulate B cells, either depleting B cells or blocking B cell functions, have been developed and evaluated in clinical trials. Belimumab, a fully humanized monoclonal antibody that specifically binds B cells activating factor (BAFF), was the first of these agents approved for SLE treatment. In this review, we explore the currently available evidence in B cell targeted therapies in SLE including agents that target B cell surface antigens (CD19, CD20, CD22), B cell survival factors (BAFF and a proliferation-inducing ligand, APRIL), cytokines (interleukin-1 and type 1 interferons) and co-stimulatory molecules (CD40 ligand). We highlighted the mechanisms of action and the individual characteristics of these biologics, and present an update on the clinical trials that have evaluated their efficacy and safety. Finally, we describe some of the emerging and promising therapies for SLE treatment.

The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort
Massimo Radin, Savino Sciascia, Doruk Erkan, Vittorio Pengo, Maria G. Tektonidou, Amaia Ugarte, Pierluigi Meroni, Lanlan Ji, H. Michael Belmont, Hannah Cohen, Guilherme Ramires de Jesus, D. Ware Branch, Paul R. Fortin, Laura Andreoli, Michelle Petri, Esther Rodriguez, Ignasi Rodriguez-Pinto, Jason S. Knight, Tatsuya Atsumi, Rohan Willis, Emilio Gonzalez, Rosario Lopez-Pedrera, Ana Paula Rossi Gandara, Margarete Borges Gualhardo Vendramini, Alessandra Banzato, Ecem Sevim, Medha Barbhaiya, Maria Efthymiou, Ian Mackie, Maria Laura Bertolaccini, Danieli Andrade, Guillermo Pons-Estel, Bill Giannakopoulos, Steve Krilis, Guilherme de Jesus, Roger Levy, Michelle Ugolini-Lopes, Renata Rosa, Danieli Andrade, Paul F. Fortin, Zhouli Zhang, Stephane Zuily, Denis Wahl, Maria Tektonidou, Cecilia Nalli, Laura Andreoli, Angela Tincani, Cecilia B. Chighizola, Maria Gerosa, Pierluigi Meroni, Alessandro Banzato, Vittorio Pengo, Savino Sciascia, Karel De Ceulaer, Stacy Davis, Olga Amengual, Tatsuya Atsumi, Imad Uthman, Maarten Limper, Ronald Derksen, Philip de Groot, Amaia Ugarte, Guillermo Ruiz Irastorza, Ignasi Rodriguez-Pinto, Ricard Cervera, Esther Rodriguez, Maria Cuadrado, Maria Angeles Aguirre Zamorano, Rosario Lopez-Pedrera, Bahar Artim-Esen, Murat Inanc, Ian Mackie, Maria Efthymiou, Hannah Cohen, Maria Laura Bertolaccini, Munther Khamashta, Giovanni Sanna, Jason S. Knight, Michelle Petri, Robert Roubey, Tom Ortel, Emilio Gonzalez, Rohan Willis, Steven Levine, Jacob Rand, H. Michael Belmont, Medha Barbhaiya, Doruk Erkan, Jane Salmon, Michael Lockshin, Ware Branch
SEMINARS IN ARTHRITIS AND RHEUMATISM, 49, 3, 464, 468, W B SAUNDERS CO-ELSEVIER INC, 2019年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis.Methods: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ("Registry"). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-beta(2) glycoprotein-1 antibodies and four for positive lupus anticoagulant test.Results: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 +/- 3.3 vs. 6 +/- 3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 +/- SD 2.9 vs. 6 +/- 3.9; p<0.05).Conclusions: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS. (C) 2019 Elsevier Inc. All rights reserved.

Factor Xa inhibitors for preventing recurrent thrombosis in patients with antiphospholipid syndrome: a longitudinal cohort study
Sato T, Nakamura H, Fujieda Y, Ohnishi N Abe N, Kono M, Kato M, Oku K, Bohgaki T, Amengual O, T, Yasuda S, Atsumi T
Lupus, 63rd, 2019年10月, ［査読有り］
英語

Circulating plasmablasts contribute to antiphospholipid antibody production, associated with type I interferon upregulation.
Ryo Hisada, Masaru Kato, Eri Sugawara, Masatoshi Kanda, Yuichiro Fujieda, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi
Journal of thrombosis and haemostasis : JTH, 17, 7, 1134, 1143, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Essentials The mechanism of antiphospholipid antibodies (aPL) production remains unclear. We investigated lymphocyte subset, single nucleotide polymorphisms (SNP), and aPL-producing cells. The increase of circulating plasmablasts was associated with type I interferon upregulation. Our novel ex vivo assay revealed circulating plasmablasts as a major source of aPL. SUMMARY: Background/objective Antiphospholipid antibodies (aPL) are pathogenic autoantibodies in antiphospholipid syndrome (APS). This study aimed to clarify the mechanism of aPL production. Methods T cell and B cell subsets were evaluated in peripheral blood mononuclear cells (PBMCs) of 26 primary APS (PAPS), 19 systemic lupus erythematosus-associated APS (SLE/APS) patients and 10 healthy controls. The SLE-related or APS-related single nucleotide polymorphisms (SNP) were analyzed in those patients. Interferon (IFN) score was calculated based on the mRNA expression of Ly6e, Mx1, IFIT1, and IFIT3 in PBMCs. The PBMCs obtained from APS patients were cultured ex vivo following depletion of CD20 positive or negative B cells and the culture supernatants were applied to aPL measurements. Results In PAPS and SLE/APS patients, Th2, Th17, and plasmablasts were increased while regulatory T, memory B, and regulatory B cells were decreased compared to healthy controls. Genetic analysis revealed that the increase of plasmablasts was more pronounced in patients carrying a risk allele of toll like receptor (TLR) 7 SNP rs3853839. The IFN score was significantly higher in the risk allele carriers. Ex vivo experiments showed that aPL were present in the culture supernatant of PBMCs lacking CD20+CD19+ subset, but not in that of cells lacking CD20-CD19+ subset. Conclusions Our data indicate an important role of plasmablasts in the production of aPL. Furthermore, the increase of plasmablasts was associated with TLR 7 and type I IFN, suggesting a common pathophysiology in SLE and APS. Targeting plasmablasts might be a novel immunological therapeutic approach in the treatment of APS.

Efficacy of dual antiplatelet therapy for preventing recurrence of arterial thrombosis in patients with antiphospholipid syndrome.
Ohnishi N, Fujieda Y, Hisada R, Nakamura H, Kato M, Oku K, Bohgaki T, Amengual O, Yasuda S, Atsumi T
Rheumatology (Oxford, England), 58, 6, 969, 974, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Warfarin is regarded as the standard treatment for preventing thrombotic events in APS, but the recurrence rate is still high. Dual antiplatelet therapy (DAPT) has been shown to be effective for the prevention of acute coronary syndrome or stroke. The objective of this study was to evaluate the efficacy of DAPT for the prevention of thrombosis recurrence in APS patients with history of arterial thrombosis. METHODS: This retrospective cohort study of APS patients was conducted at Hokkaido University Hospital between 1990 and 2016. The secondary prophylactic effects and safety of warfarin monotherapy (Wf), antiplatelet monotherapy (AP), warfarin and antiplatelet combination therapy (Wf + AP) and DAPT were evaluated. The primary endpoints were set as thrombosis-free and adverse events-free survival period. Adverse events were defined as severe bleeding and death. RESULTS: A total of 90 APS patients were enrolled. Thrombotic recurrence was found in 40 patients (35 arterial and 5 venous thromboses) and serious adverse events in 20 patients (9 severe bleeding events and 14 deaths). Kaplan-Meier analysis demonstrated a 10-year recurrence-free survival rate of 62%. The recurrence rate per 100 patient-years was as follows: Wf: 11.6, AP: 5.5, Wf: + AP: 3.7, DAPT: 1.8. We demonstrated that DAPT significantly reduced the rate of recurrence compared with Wf (log-rank P = 0.001). There were no significant differences in the rate of serious adverse events among the groups. CONCLUSION: DAPT might be considered as an effective and safe option for the prophylaxis of recurrent arterial thrombosis in APS.

Pathogenic roles of anti-C1q antibodies in recurrent pregnancy loss.
Kazumasa Ohmura, Kenji Oku, Tamao Kitaori, Olga Amengual, Ryo Hisada, Masatoshi Kanda, Yuka Shimizu, Yuichiro Fujieda, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Mayumi Sugiura-Ogasawara, Tatsuya Atsumi
Clinical immunology (Orlando, Fla.), 203, 37, 44, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Recurrent pregnancy loss (RPL) is often considered idiopathic, however excessive complement activation has been observed in pregnancy related manifestations. Anti-C1q antibodies (anti-C1q) are associated with the activation of complement pathway in lupus patients, while it remains unclear in RPL. Firstly, we showed that both the prevalence and titre of anti-C1q were significantly higher in unexplained RPL than in healthy parous individuals. Secondly, we established the murine model of anti-C1q induced pregnancy loss using a monoclonal anti-mouse C1q antibody, JL-1. In mice treated with JL-1, high ratio of pregnancy loss and fetal growth restriction were frequently observed and complement activation occurred. C5a receptor (C5aR) blockade cancelled these pathogenic changes in mice treated with JL-1. In conclusion, our study reveals an association between the prevalence of anti-C1q and RPL. Additionally, our murine model has indicated that anti-C1q can induce reproductive failure, which might be ameliorated by therapy targeting the C5-C5aR axis.

Disseminated subcutaneous nodules and destructive polyarthritis.
Nobuya Abe, Yuichiro Fujieda, Olga Amengual, Tatsuya Atsumi
BMJ (Clinical research ed.), 365, l1344, 2019年04月17日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Antiphospholipid score is a novel risk factor for idiopathic osteonecrosis of the femoral head in patients with systemic lupus erythematosus.
Hisada R, Kato M, Ohnishi N, Sugawara E, Fujieda Y, Oku K, Bohgaki T, Amengual O, Yasuda S, Atsumi T
Rheumatology (Oxford, England), 58, 4, 645, 649, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Idiopathic osteonecrosis of the femoral head (ION) is a common complication of SLE associated with CS therapy. Although the pathogenesis of ION involves local bone ischaemia favoured by thrombophilia, the involvement of aPL in lupus ION remains to be elucidated. We have previously reported the aPL score (aPL-S) as a quantitative marker of aPL and the development of thrombotic events in autoimmune diseases. The aim of this study was to identify the impact of aPL on the development of ION using aPL-S. METHODS: This was a single-centre retrospective study comprising 88 consecutive SLE patients who underwent MRI of the hip joints from January 2000 to March 2017. Baseline characteristics, pharmacotherapy and total hip arthroplasty performed during follow-up were evaluated. RESULTS: The presence of ION was confirmed by MRI scan in 38 patients (43.1%). Male gender, positivity of any aPL, aPL-S, high aPL-S (≥30) and high dose of CS were identified as risk factors for ION by univariate analysis. Multivariate analysis revealed high aPL-S (odds ratio 5.12, 95% CI 1.18-29.79) and use of high-dose CS (odds ratio 10.25, 95% CI 3.00-48.38) as independent variables. Kaplan-Meier analysis showed that patients with high aPL-S received total hip arthroplasty more frequently than those without aPL (P = 0.010). CONCLUSIONS: We newly identified high aPL-S as an important risk factor for ION development in SLE, suggesting the involvement of aPL-induced coagulopathy in the pathophysiology of lupus ION.

強皮症-2 疾患特異的iPS細胞を用いた強皮症性肺動脈性肺高血圧症の病態解明　　　　　　　　　　　　　　　
工藤 友喜, 加藤 将, 柴田 悠平, 神田 真聡, リー・ウェンシー, 河野 通大, 菅原 恵理, 河野 通仁, 藤枝 雄一郎, 坊垣 暁之, アメングアル・オルガ, 奥 健志, 保田 晋助, 渥美 達也
日本リウマチ学会総会・学術集会プログラム・抄録集, 63回, 539, 539, (一社)日本リウマチ学会, 2019年03月
日本語

Potential therapeutics for antiphospholipid antibody associated thrombocytopenia: a systematic review and meta-analysis.
Abe N, Oku K, Amengual O, Fujieda Y, Kato M, Bohgaki T, Yasuda S, Mori R, Morishita E, Suzuki-Inoue K, Atsumi T
Modern rheumatology, 30, 1, 1, 21, Informa UK Limited, 2018年12月, ［査読有り］
研究論文（学術雑誌）

Pathogenic role of antiphospholipid antibodies: an update
Y. Fujieda, O. Amengual, T. Atsumi
Lupus, 27, 13, 2012, 2013, SAGE Publications Ltd, 2018年11月01日
英語, 研究論文（学術雑誌）

Pathogenesis of Antiphospholipid syndrome:and update　　　　　　　　　　　　　　　
アメングアル オルガ
Lupus, 2018年10月, ［査読有り］, ［招待有り］
英語

Clinical significance of plasma presepsin levels in patients with systemic lupus erythematosus.
Shun Tanimura, Yuichiro Fujieda, Michihiro Kono, Yuhei Shibata, Ryo Hisada, Eri Sugawara, Hiroyuki Nakamura, Kazumasa Ohmura, Sanae Shimamura, Asako Mitani, Haruki Shida, Toshiyuki Watanabe, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Shinsuke Yasuda, Chikara Shimizu, Tatsuya Atsumi
Modern rheumatology, 28, 5, 865, 871, 2018年09月, ［査読有り］, ［国際誌］
英語, OBJECTIVES: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SLE. METHODS: This retrospective study comprised 35 patients with SLE and 72 with non-SLE autoimmune diseases who visited our facility during the period from August 2012 to September 2015. Plasma PSEP levels and laboratory data were compared between SLE and non-SLE. Clinical markers of SLE disease activity, including SLE disease activity index 2000 (SLEDAI-2K), serum complement concentrations and serum anti-ds-DNA antibodies were assessed in correlation with plasma PSEP levels. RESULTS: Plasma PSEP levels in SLE were higher than those in non-SLE. This phenomenon holds true when comparing SLE and non-SLE patients in the absence of infection (p = .0008). Plasma PSEP levels in SLE patients negatively correlated with C3 (r = -0.4454, p = .0430), CH50 (r = -0.4502, p = .0406) and positively with SLEDAI-2K (r = 0.4801, p = .0237). CONCLUSION: Elevated plasma PSEP levels were correlated with disease activity of SLE, suggesting inappropriate monocyte or neutrophil activation in the pathophysiology of SLE exacerbation.

Women and Science　　　　　　　　　　　　　　　
García-Martín F, Rosich M, de Vega S, San Gabriel A, Amengual O
Journal of Science and Humanities Areces Foundation, 19, 111, 121, 2018年07月, ［招待有り］
スペイン語

Antiphospholipid syndrome, “the best prophet of the future”
Olga Amengual, Tatsuya Atsumi
Modern Rheumatology, 28, 3, 409, 416, Taylor and Francis Ltd, 2018年05月04日, ［査読有り］, ［招待有り］
英語, The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of venous and arterial thromboses, often multiple, and obstetric-related adverse events in the presence of antiphospholipid antibodies (aPL). APS, first described in 1983, as thrombosis, abortion and cerebral disease, is nowadays recognised as a systemic disease with a wide constellation of clinical manifestations related to acute and chronic vascular lesions. The presence of aPL is the serological hallmark of APS representing a heterogeneous population of autoantibodies with many antigenic specificities directed to phospholipid-binding proteins, either alone or in combination with phospholipids. Many assays have been developed for aPL detection. Particularly, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant are essential tools for APS diagnosis. The cumulative evidence indicates that aPL are pathogenic autoantibodies binding to target cells and promoting thrombosis and pregnancy complications through a wide range of pathological mechanisms not yet fully understood. Finally, the recognition of the important role of aPL to assess the individual risk of thrombosis or pregnancy complications has expanded the concept of aPL, and currently aPL profile is regarded as a major risk factor for clinical thrombotic events.

Alternative pathway activation due to low level of complement factor H in primary antiphospholipid syndrome.
Hiroyuki Nakamura, Kenji Oku, Yusuke Ogata, Kazumasa Ohmura, Yoko Yoshida, Etsuko Kitano, Yuichiro Fujieda, Masaru Kato, Toshiyuki Bohgaki, Olga Amengual, Shinsuke Yasuda, Yoshihiro Fujimura, Tsukasa Seya, Tatsuya Atsumi
Thrombosis research, 164, 63, 68, 2018年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Although complement activation has been proposed as a possible thrombophilic mechanism in antiphospholipid syndrome (APS), the origin of complement activation in APS remains unclear. Here, we focused on complement regulatory factors (CRF), which control the complement system to prevent damage to host tissue. We evaluated the function of two major CRF, membrane cofactor protein (MCP) and factor H (FH), in APS patients. MATERIALS AND METHODS: In this study, we analyzed preserved serum samples from 27 patients with primary APS (PAPS), 20 with APS complicated with SLE (APS + SLE), 24 with SLE (SLE), and 25 with other connective tissue diseases (Other CTD). Serum MCP and FH levels were tested by ELISA. Autoantibodies against FH were determined by both ELISA and western-blotting. RESULTS: Serum complement levels of PAPS were lower than those of other CTD (median C3: 82 vs 112 mg/dL, p < 0.01, C4: 15 vs 22 mg/dL, p < 0.05). Serum MCP levels did not significantly differ among the groups. Serum FH levels were significantly lower in PAPS patients compared with SLE or other CTD (median 204, 1275, and 1220 μg/mL, respectively, p < 0.01). In PAPS patients, serum FH levels were positively correlated with serum C3 levels (p < 0.01, R = 0.55), but no correlation was found with serum C4 levels (p = 0.22, R = 0.33). Autoantibodies against FH were not detected in any of our patients. CONCLUSIONS: Activation of the alternative complement pathway due to low level of FH is one of the possible thrombophilic mechanisms in PAPS.

First-Line, Non-Criterial Antiphospholipid Antibody Testing for the Diagnosis of Antiphospholipid Syndrome in Clinical Practice: A Combination of Anti-β2 -Glycoprotein I Domain I and Anti-Phosphatidylserine/Prothrombin Complex Antibodies Tests.
Hiroyuki Nakamura, Kenji Oku, Olga Amengual, Kazumasa Ohmura, Yuichiro Fujieda, Masaru Kato, Toshiyuki Bohgaki, Shinsuke Yasuda, Tatsuya Atsumi
Arthritis care & research, 70, 4, 627, 634, 2018年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To assess the value of a combination of anti-β2 -glycoprotein I (anti-β2 GPI) domain I antibody and anti-phosphatidylserine/prothrombin complex (anti-PS/PT) antibody tests for the diagnosis of antiphospholipid syndrome (APS). METHODS: This cross-sectional study involved a cohort of the patients who visited our clinic from April 2005 to March 2013. Tests for anti-β2 GPI domain I antibodies, IgG anti-PS/PT antibodies, and IgM anti-PS/PT antibodies, together with tests for criteria-defined antiphospholipid antibodies (aPL), were performed in all patients. The total antiphospholipid score (aPL-S) was calculated for each patient according to titers of and positivity for aPL. RESULTS: The study enrolled 157 patients (51 patients with APS and 106 with non-APS autoimmune diseases). All 21 patients positive for both anti-β2 GPI domain I antibodies and IgG and/or IgM (IgG/IgM) anti-PS/PT antibodies had APS with a high total aPL-S (median 46, range 26-76), as did all of the 10 patients who were positive for anti-β2 GPI domain I antibodies but negative for IgG/IgM anti-PS/PT antibodies (median 22, range 4-39). Of the 14 patients who were positive for IgG/IgM anti-PS/PT antibodies but negative for anti-β2 GPI domain I antibodies, 11 (79%) had APS; these individuals also had high total aPL-S values (median 23, range 11-60). In contrast, only 9 of the 112 patients (8%) with none of these antibodies had APS. CONCLUSION: The combination of the IgG anti-β2 GPI domain I antibody and IgG/IgM anti-PS/PT antibody tests shows a high positive predictive value for the diagnosis of APS and a strong correlation with the aPL-S. This combination as the first-line test for aPL may contribute to the simple and definite identification of APS with a high risk of thrombosis in clinical practice.

Effects of statins on thrombosis development in patients with systemic lupus erythematosus and antiphospholipid antibodies
T. Watanabe, K. Oku, O. Amengual, R. Hisada, K. Ohmura, I. Nakagawa, H. Shida, T. Bohgaki, T. Horita, S. Yasuda, T. Atsumi
Lupus, 27, 2, 225, 234, SAGE Publications Ltd, 2018年02月01日, ［査読有り］
英語, 研究論文（学術雑誌）, The objective of this study is to identify the effects of statins and risk factors for thrombosis in patients with new onset of systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL). Consecutive patients with SLE without history of thrombotic events were retrospectively enrolled from April 1997 to February 2014. The development of first thrombosis and death caused by thrombosis were defined as the study endpoint. Risk and protective factors for developing thrombosis were analyzed. A total of 152 patients, 80 positive and 72 negative for aPL, were included. In aPL-positive patients, 15 developed arterial (n = 6) and venous (n = 9) thrombosis (median follow-up period 69 months). Cox’s proportional hazards model showed that older age at SLE onset and IgG-anticardiolipin antibodies (aCL) were statistically significant risks for thrombosis. Statin therapy was identified as a statistically significant protective factor against thrombosis (hazard ratio 0.12, 95% confidence interval 0.01–0.98). In aPL-negative patients (median follow-up period 46 months), seven patients developed thrombosis (five arterial and two venous). No risk factors for thrombosis were found in this group. In aPL-positive patients with SLE, the late disease onset and the presence of IgG-aCL represented additional risk factors for thrombosis. Statin treatment appeared as a protective factor for thrombosis.

Thrombotic risk stratification by platelet count in patients with antiphospholipid antibodies: a longitudinal study
R. Hisada, M. Kato, E. Sugawara, Y. Fujieda, K. Oku, T. Bohgaki, O. Amengual, S. Yasuda, T. Atsumi
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 15, 9, 1782, 1787, WILEY, 2017年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome. However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers.
Objectives To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers, and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titers.
Patients/methods A single-center, retrospective, longitudinal study comprising 953 consecutive patients who were suspected of having autoimmune disease between January 2002 and December 2006 was performed. Low platelet count was defined as a count of < 150 x 10(3) L-1 at the time of aPL testing.
Results A negative correlation was observed between aPL-S and platelet count (r = - 0.2477). Among aPL-positive patients, those with a low platelet count developed thrombosis more frequently than those without (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.11-7.88). Among aPL-negative patients, no difference was found in the predictive value of thrombosis regardless of platelet count. Patients with aPLs were further divided into two subgroups according to aPL-S. Among low-aPL-S patients, those with low platelet counts developed thrombosis more frequently than those without (HR 3.44, 95% CI 1.05-11.2). In contrast, high-aPL-S patients developed thrombosis frequently regardless of platelet count.
Conclusions aPL carriers with low platelet counts are at high risk of developing thrombosis. In particular, low-aPL-S carriers' may be stratified by platelet count in terms of predicting future thrombotic events.

How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of Validated Scores
Kenji Oku, Olga Amengual, Shinsuke Yasuda, Tatsuya Atsumi
CURRENT RHEUMATOLOGY REPORTS, 19, 8, 51, SPRINGER, 2017年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose of Review Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have procoagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population.
Recent Findings It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Antiphospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserinedependent antiprothrombin antibodies (aPS/PT).
Summary Additionally, clinicians may need to be aware of the patient's medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.

Acute aortic thrombosis related to antiphospholipid antibodies
H. Nakamura, O. Amengual, T. Horita, M. Kato, K. Oku, T. Bohgaki, S. Yasuda, T. Atsumi
LUPUS, 26, 7, 783, 784, SAGE PUBLICATIONS LTD, 2017年06月, ［査読有り］
英語

SLE・抗リン脂質抗体症候群 活動性ループス腎炎に対する中等量ステロイド併用ミコフェノール酸モフェチルによる寛解導入療法の有効性　　　　　　　　　　　　　　　
河野 通大, 保田 晋助, 阿部 早和子, 大西 直樹, 土井 基嗣, 谷村 瞬, 久田 諒, 菅原 恵理, 中村 浩之, 大村 一将, 嶋村 抄苗, 清水 裕香, 藤枝 雄一郎, 加藤 将, 奥 健志, 坊垣 暁之, アメングアル・オルガ, 渥美 達也
日本リウマチ学会総会・学術集会プログラム・抄録集, 61回, 460, 460, (一社)日本リウマチ学会, 2017年03月, ［査読有り］
日本語

Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study
O. Amengual, R. Forastiero, M. Sugiura-Ogasawara, K. Otomo, K. Oku, C. Favas, J. Delgado Alves, P. Zigon, A. Ambrozic, M. Tomsic, I. Ruiz-Arruza, G. Ruiz-Irastorza, M. L. Bertolaccini, G. L. Norman, Z. Shums, J. Arai, A. Murashima, A. E. Tebo, M. Gerosa, P. L. Meroni, I. Rodriguez-Pinto, R. Cervera, J. Swadzba, J. Musial, T. Atsumi
LUPUS, 26, 3, 266, 276, SAGE PUBLICATIONS LTD, 2017年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis.
Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards.
Results In the initial study (n=247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed (k=0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p<0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study (n=214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed (k=0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p<0.0001. Sensitivity, specificity, LR+and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively.
Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.

P1-18 オートファジーは滑膜線維芽細胞においてビメンチンのシトルリン化を促進する
菅原 恵理, 加藤 将, 久田 諒, 藤枝 雄一郎, 奥 健志, 坊垣 暁之, アメングアル オルガ, 渥美 達也
日本臨床免疫学会会誌, 40, 4, 302b, 302b, 日本臨床免疫学会, 2017年
日本語,

【目的】関節リウマチ（Rheumatoid arthritis: RA）の滑膜線維芽細胞（Fibroblast like synoviocytes: FLS）におけるオートファジーとビメンチンのシトルリン化の関連を明らかにする．【方法】6名のRAの患者血清の抗シトルリン化ビメンチン抗体価をELISA法で測定した．ヒト滑膜組織から分離したFLSをプロテアソーム阻害薬のMG132および無血清培地による飢餓状態で刺激しオートファジーを誘導した．オートファジーおよび細胞内のシトルリン化ビメンチンを抗LC3抗体，抗シトルリン抗体，抗ビメンチン抗体，抗β-アクチン抗体，抗シトルリン化ビメンチン抗体陽性患者血清を一次抗体として用いたウエスタンブロット法で評価した．【結果】抗シトルリン抗体，抗ビメンチン抗体，抗シトルリン化ビメンチン抗体陽性患者血清は54 kDaのタンパクを認識し，FLS内のビメンチンのシトルリン化が示唆された．24時間の10 μMのMG132刺激および，2-3時間の飢餓状態でLC3-IIおよびシトルリン化蛋白が有意に増加したが，ビメンチンの蛋白量は増加せず，オートファジー誘導によりビメンチンのシトルリン化の亢進が示唆された．【結論】オートファジーはFLSにおけるビメンチンのシトルリン化を促進し，RAの病態形成に関与している可能性がある．

P1-19 抗リン脂質抗体症候群における末梢血リンパ球サブセット解析および抗体産生機序の解明
久田 諒, 加藤 将, 菅原 恵理, 藤枝 雄一郎, 奥 健志, 坊垣 暁之, Amengual Olga, 保田 晋助, 渥美 達也
日本臨床免疫学会会誌, 40, 4, 302c, 302c, 日本臨床免疫学会, 2017年
日本語,

【背景/目的】抗リン脂質抗体症候群（APS）において抗リン脂質抗体（aPL）は病原性を有する自己抗体とされるが，その産生機序については不明な点が多い．今回，APS患者における末梢血リンパ球サブセットを行い，更に末梢血単核球細胞（PBMC）をex vivoの系で刺激しaPL産生能をもつ細胞の同定を試みるアプローチを行った．【方法】原発性抗リン脂質抗体症候群（PAPS）患者，全身性エリテマトーデス続発性抗リン脂質抗体症候群（SLE/APS）患者，健常者の3群について，リンパ球サブセット解析を行い比較した．次にCD20 microbeadsを用いてCD20陽性細胞を除去したAPS患者のPBMCを刺激・培養し，培養上清中のaPLをELISA法及びcell-based assayにより測定した．【結果】PAPS群18名，SLE/APS群8名，健常者群8名についてサブセット解析を行った．Pre-switched memory B cell（p = 0.030），post-switched memory B cell（p = 0.032）はPAPS群で健常者群と比べ有意に減少していた．また，一部のAPS患者のPBMC培養上清からaPL-IgG（ELISA），aPL-IgM（cell-based assay）が検出され，CD20陽性細胞を除去したPBMCの培養上清中からもaPL-IgG，aPL-IgMが検出された．【結論】PAPS患者においてpre-switched memory B cellとpost-switched memory B cellの減少が見られた．また，aPL産生にCD20陰性B細胞が寄与している可能性が示唆された．

Effectiveness of a Medical English Course on Communication Abilities of Graduate Medical Students　　　　　　　　　　　　　　　
アメングアル オルガ
Medical Science Educator Journal, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）

Current trends in medical English education and the Japan College of Rheumatology International School
Eric Hajime Jego, Olga Amengual
MODERN RHEUMATOLOGY, 27, 6, 1101, 1105, TAYLOR & FRANCIS LTD, 2017年, ［査読有り］
英語, In light of the present revolution happening in medical education in Japan as medical schools implement new curricula to conform to global standards, there is a growing demand for more internationalization and higher quality practical medical English education. In response, many institutions including governmental organizations, universities and academic associations are moving ahead with new initiatives to adapt to these changing demands. This paper reviews the current trends and innovations in medical English education in Japan. This paper also describes one initiative by the Japan College of Rheumatology (JCR) known as the JCR International School held yearly in Karuizawa. By examining recent trends and innovations in medical English education in Japan, the most relevant and applicable can be elucidated to illuminate a path forward for improved medical English education within the JCR.

Effectiveness of whole-body magnetic resonance imaging for the efficacy of biologic anti-rheumatic drugs in patients with rheumatoid arthritis: A retrospective pilot study
Michihito Kono, Tamotsu Kamishima, Shinsuke Yasuda, Keita Sakamoto, Sawako Abe, Atsushi Noguchi, Toshiyuki Watanabe, Yuka Shimizu, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Tatsuya Atsumi
MODERN RHEUMATOLOGY, 27, 6, 953, 960, TAYLOR & FRANCIS LTD, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs).Methods: Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed before and 1 year after bDMARDs initiation.Results: At baseline, mean age was 57.1 years and mean disease duration was 3.0 years. Median disease activity score in 28 joints improved from 5.1 to 2.1. Treatment with bDMARDs improved mean whole-body synovitis score from 31.2 to 23.2 and median whole-body bone-edema score from 11 to 3. Whole-body bone-erosion score improved in seven patients and deteriorated in 17 patients. Logistic regression analysis identified whole-body synovitis score as a poor prognostic factor for whole-body bone-erosion progression. Bone-edema score in individual bones was identified as a poor prognostic factor for the progression of bone-erosion. Changes in hand synovitis score correlated with those of other joints, but neither changes in bone-edema nor erosion score of hands correlated with those of other joints in WBMRI.Conclusions: WBMRI scoring may be a novel useful tool to evaluate the efficacy of anti-rheumatic drugs, as well as a potential predictor of joint prognosis, in patients with RA.

Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-β2 glycoprotein i antibodies
K. Otomo, O. Amengual, Y. Fujieda, H. Nakagawa, M. Kato, K. Oku, T. Horita, S. Yasuda, M. Matsumoto, K. I. Nakayama, S. Hatakeyama, T. Koike, Tatsuya Atsumi
Lupus, 25, 12, 1288, 1298, SAGE PUBLICATIONS LTD, 2016年10月
英語, 研究論文（学術雑誌）, © The Author(s), 2016. Objective The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by β2GPI-dependent anticardiolipin antibody (aCL/β2GPI) on monocytes. Methods Human serum incubated with FLAG-β2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed. Results Apolipoprotein B100 (APOB) was the only identified serum molecule in the MS search. Oxidized LDL, containing APOB as well as ox-Lig1 (a known ligand of β2GPI), was revealed as a β2GPI-binding molecule in the immunoprecipitation assay. TF mRNA was markedly induced by oxidized LDL/β2GPI complexes with either WBCAL-1 (monoclonal aCL/β2GPI) or purified IgG from APS patients. The activities of lipoprotein-associated phospholipase A2, one of the component molecules of oxidized LDL, were significantly higher in serum from APS patients than in those from controls. Conclusion APOB (or oxidized LDL) was detected as a major β2GPI binding serum molecule by LC-MS search. Oxidized LDL/aCL/β2GPI complexes significantly induced TF expressions on monocytes. These data suggest that complexes of oxidized LDL and aCL/β2GPI may have a crucial role in the pathophysiology of APS.

Complement and thrombosis in the antiphospholipid syndrome
Kenji Oku, Hiroyuki Nakamura, Michihiro Kono, Kazumasa Ohmura, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Olga Amengual, Tatsuya Atsumi
AUTOIMMUNITY REVIEWS, 15, 10, 1001, 1004, ELSEVIER SCIENCE BV, 2016年10月, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）, The involvement of complement activation in the pathophysiology of antiphospholipid syndrome (APS) was first reported in murine models of antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously reported that complement activation is prevalent and may function as a source of procoagulant cell activation in the sera of APS patients. Recently, autoantibodies against C1q, a component of complement 1, were reported to be correlated with complement activation in systemic lupus erythematosus. These antibodies target neoepitopes of deformed C1q bound to various molecules (i.e., anionic phospholipids) and induce accelerated complement activation. We found that anti-C1q antibodies are more frequently detected in primary APS patients than in control patients and in refractory APS patients with repeated thrombotic events. The titer of anti-C1q antibodies was significantly higher in refractory APS patients than in APS patients without flare. The binding of C1q to anionic phospholipids may be associated with the surge in complement activation in patients with anti-C1q antibodies when triggered by 'second-hit' biological stressors such as infection. Such stressors will induce overexpression of anionic phospholipids, with subsequent increases in deformed C1q that is targeted by anti-C1q antibodies. (C) 2016 Published by Elsevier B.V.

Significance of fully automated tests for the diagnosis of antiphospholipid syndrome
Kenji Oku, Olga Amengual, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Naoya Sakamoto, Masahiro Ieko, Gary L. Norman, Tatsuya Atsumi
THROMBOSIS RESEARCH, 146, 1, 6, PERGAMON-ELSEVIER SCIENCE LTD, 2016年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Antiphospholipid antibodies (aPLs) can vary both immunologically and funcLionally, thus i is important to effectively and correctly identify their presence when diagnosing antiphospholipid syndrome. Furthermore, since many immunologicallfunclional tests are necessary Lo measure aPLs, complete examinations are often no performed in many cases due o significath burden on the testing departments. To address this issue, we measured aPLs defined accordingio the classification criteria (anlicardiolipin araibody: aCL) IgG/IgM and anti-132 glycoprotein I antibody (a beta(2)GPI) (IgG/IgM) as well as non-criteria antibodies (aCL IgA, a beta(2)GPI IgA and a beta(2)GPI domain I), in a cohort 01 211 patients (61 APS, 140 disease controls and 10 healthy individuals). APLs were measured using a fully automated chemiluminescent immunoassay instrument (BIO-FLASH (R)/ACL AcuStara (R)) and with conventional ELISA tests. We demonstrated that both sensitivity and accuracy of diagnosis of aCL IgG and beta(2)GPI IgG were high, in agreement with the past reports. When multiple aPLs were examined, the accuracy of diagnosis increased. The proportion of APS patients that were positive for 2 Of more types of aPLs (47/61, 77%) was higher than that of patients with systemic lupus erythematosus (SLE)( 3/37, 9%), those with non-SLE connective tissues diseases (1/53,2%), those with other diseases or healthy volunteers. Based on these findings, it was concluded that the fully automated chemiluminescent immunoassay instrument, which allows the simultaneous evaluation of many types of aPLs, offers clear advantages for a more complete, more rapid and less labor-intensive alternative to running multiple ELISA and could help in better diagnosis for suspected APS patients. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (thip://creativecommons.orglicenscs,thy-nc-nd/4.0,/).

Autoantibodies against a complement component 1 q subcomponent contribute to complement activation and recurrent thrombosis/pregnancy morbidity in anti-phospholipid syndrome
Kenji Oku, Olga Amengual, Ryo Hisada, Kazumasa Ohmura, Ikuma Nakagawa, Toshiyuki Watanabe, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi
RHEUMATOLOGY, 55, 8, 1403, 1411, OXFORD UNIV PRESS, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. To investigate the prevalence and significance of the autoantibodies against complement component 1 q subcomponent (C1q) in patients with APS.
Methods. In all, 40 consecutive primary APS patients, 42 patients with non-SLE CTDs and 20 SLE patients negative for aPL were enrolled in this retrospective analysis. Refractory APS was defined as a clinical status of recurring thrombosis or pregnancy morbidity during adequate secondary prophylaxis. An ELISA was used to measure serum levels of anti-C1q antibodies and anaphylatoxins (C3a, C4a).
Results. Anti-C1q antibodies were found in 36% (15/42) and 2.5% (1/40) of primary APS patients and controls, respectively. Among primary APS patients, anti-C1q antibody titres were significantly correlated with serum C4a levels (P = 0.013). Neither the prevalence nor the titre of anti-C1q antibodies was associated with any specific clinical manifestations of APS, nor titres of aPL. Refractory APS patients (n = 10) had a higher prevalence of anti-C1q antibodies (9/10 vs 6/32, P = 0.01) than APS patients without recurrence (n = 32).
Conclusion. Anti-C1q antibodies are associated with complement activation in APS and may contribute to the pathogenesis, particularly in refractory cases.

Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes
Yuichiro Fujieda, Olga Amengual, Masaki Matsumoto, Kimiko Kuroki, Hidehisa Takahashi, Michihito Kono, Takashi Kurita, Kotaro Otomo, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Katsumi Maenaka, Shigetsugu Hatakeyama, Keiichi I. Nakayama, Tatsuya Atsumi
RHEUMATOLOGY, 55, 6, 1117, 1126, OXFORD UNIV PRESS, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Phosphatidylserine-dependent, also called aPS-PT, recognizes the phosphati dylserine-prothrombin complex, which is associated with APS. We have previously reported that aPS-PT induces tissue factor (TF) expression on monocytes through the p38 mitogen-activated protein kinase pathway. However, the cell surface interaction between prothrombin and aPS-PT, which is involved in the activation of cell-signalling pathways, has remained unknown. The objective of this study was to identify membrane proteins involved in the binding of prothrombin and aPS-PT to monocyte surfaces as well as the induction of TF expression.
Methods. RAW264.7 cells with FLAG-tagged prothrombin were incubated and separated using affinity chromatography with anti-FLAG antibody-conjugated Sepharose beads. Immunopurified proteins were then analysed by an online nano-liquid chromatography-tandem mass spectrometry. The binding between prothrombin and the identified protein, ribophorin II (RPN2), was analysed by ELISA and surface plasmon resonance. To elucidate the role of RPN2 in TF expression, the TF mRNA level in RAW264.7 cells treated with RPN2 small interfering RNA was determined by quantitative real-time PCR (qPCR).
Results. RPN2 was identified as a candidate molecule involved in the binding of prothrombin to the cell surface. The binding between prothrombin and RPN2 was confirmed by ELISA and surface plasmon resonance. RAW264.7 cells treated with RPN2 small interfering RNA showed significant reduction of the TF expression mediated by prothrombin and a mouse monoclonal aPS-PT.
Conclusion. We identified that RPN2 is one of the prothrombin-binding proteins on monocyte surfaces, suggesting that RPN2 is involved in the pathophysiology of thrombosis in patients with APS.

Markers of thrombotic events in autoimmune diseases: Comparison of Antiphospholipid Score (aPL-S) and Global Anti-phospholipid Syndrome Score (GAPSS)
Kenji Oku, Olga Amengual, Hiroyuki Nakamura, Ryo Hisada, Kazumasa Oomura, Masaru Mato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 112, 129, 130, ELSEVIER IRELAND LTD, 2015年11月, ［査読有り］
英語

Educational improvement in Medical English Practice: Questionnaire survey to sophomore medical students of Hokkaido University.
Murakami M, Olga A, Iguchi K, Otaki J
[Hokkaido igaku zasshi] The Hokkaido journal of medical science, 90, 2, 99, 104, 2015年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, In the past, we made several efforts making curriculum changes to Medical English Practice, however, these changes did not improve motivation effectively. We have completely modified the curriculum in 2012, and performed a questionnaire survey to 112 sophomore medical students. In the final exam, students answered a questionnaire assessing all classes of the course by scoring 3 points (no change required), 2 points (minor change required), and 1 point (major change required or discontinue). In addition, students could write free comments about potential contents they would like to add to the curriculum. Each class was assessed as more than or equal to 2.5 points on average (range: 2.50-2.96). Potential contents students want to add are: 1. Speaking (45 students [55%]), 2. Listening (30 students [37%]), 3. Reading (6 students [7%]), 4. Writing (1 student [1%]). The most frequent suggestion was to include group discussions in speaking (27 students [33%]), followed by listening on topics of healthcare systems (11 students [13%]). Many students suggested to include conversation classes in small groups, or classes in which international students introduce the structure of healthcare systems of their home countries to the curriculum. Increasing the participation of international faculty, staff and students in the Medical English Practice might contribute to the improvement of medical students' motivation.

Primary prophylaxis to prevent obstetric complications in asymptomatic women with antiphospholipid antibodies: a systematic review
O. Amengual, D. Fujita, E. Ota, L. Carmona, K. Oku, M. Sugiura-Ogasawara, A. Murashima, T. Atsumi
LUPUS, 24, 11, 1135, 1142, SAGE PUBLICATIONS LTD, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: Obstetric complications are common in patients with antiphospholipid syndrome. However, the impact of antiphosholipid antibodies (aPL) in the pregnancy outcomes of asymptomatic aPL carriers is uncertain. The aim of this systematic review is to assess whether primary prophylaxis is beneficial to prevent obstetric complications during pregnancy in asymptomatic women positive for aPL who have no history of recurrent pregnancy loss or intrauterine fetal death. Methods: Studies evaluating the effect of prophylactic treatment versus no treatment in asymptomatic pregnant aPL carriers were identified in an electronic database search. Design, population and outcome homogeneity of studies was assessed and meta-analysis was performed. The pooled Mantel-Haenszel relative risk of specific pregnancy outcomes was obtained using random effects models. Heterogeneity was measured with the I 2 statistic. All analyses were conducted using Review Manager 5.3. Results: Data from five studies involving 154 pregnancies were included and three studies were meta-analysed. The risk ratio and 95% confidence interval (CI) of live birth rates, preterm birth, low birth weight and overall pregnancy complications in treated and untreated pregnancies were 1.14 (0.18-7.31); 1.71 (0.32-8.98); 0.98 (0.07-13.54) and 2.15 (0.63-7.33), respectively. Results from the meta-analysis revealed that prophylactic treatment with aspirin is not superior to placebo to prevent pregnancy complications in asymptomatic aPL carriers. Conclusion: This systematic review did not find evidence of the superiority of prophylactic treatment with aspirin compared to placebo or usual care to prevent unfavourable obstetric outcomes in otherwise healthy women with aPL during the first pregnancy.

The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis.
Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Amengual O, Horita T, Atsumi T
Rheumatology (Oxford, England), 54, 8, 1536, 1536, 2015年08月, ［査読有り］, ［国際誌］
英語

An independent validation of the Global Anti-Phospholipid Syndrome Score in a Japanese cohort of patients with autoimmune diseases
K. Oku, O. Amengual, T. Bohgaki, T. Horita, S. Yasuda, T. Atsumi
LUPUS, 24, 7, 774, 775, SAGE PUBLICATIONS LTD, 2015年06月, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）

Ras Guanine Nucleotide-Releasing Protein 4 Is Aberrantly Expressed in the Fibroblast-like Synoviocytes of Patients With Rheumatoid Arthritis and Controls Their Proliferation
Michihito Kono, Shinsuke Yasuda, Richard L. Stevens, Hideyuki Koide, Takashi Kurita, Yuka Shimizu, Yusaku Kanetsuka, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Tomohiro Shimizu, Tokifumi Majima, Takao Koike, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 67, 2, 396, 407, WILEY, 2015年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Ras guanine nucleotide-releasing protein 4 (RasGRP-4) is a calcium-regulated guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor not normally expressed in fibroblasts. While RasGRP-4-null mice are resistant to arthritis induced by anti-glucose-6-phosphate isomerase autoantibodies, the relevance of these findings to humans is unknown. We undertook this study to evaluate the importance of RasGRP-4 in the pathogenesis of human and rat arthritis.
Methods. Synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were evaluated immunohistochemically for the presence of RasGRP-4 protein. Fibroblast-like synoviocytes (FLS) were isolated from synovial samples, and expression of RasGRP-4 was evaluated by real-time quantitative reverse transcription-polymerase chain reaction analyses. The proliferation potency of FLS was evaluated by exposing the cells to a RasGRP-4-specific small interfering RNA (siRNA). Finally, the ability of RasGRP-4-specific siRNAs to hinder type II collagen-induced arthritis in rats was evaluated to confirm the importance of the signaling protein in the disease.
Results. Unexpectedly, RasGRP-4 protein was detected in the synovial hyperplastic lining, where proliferating FLS preferentially reside. FLS isolated from tissues obtained from a subpopulation of RA patients expressed much more RasGRP-4 than did FLS from examined OA patients. Moreover, the level of RasGRP-4 transcript was correlated with the FLS proliferation rate. The ability of cultured FLS to divide was diminished when they were treated with RasGRP-4-specific siRNAs. The intraarticular injection of RasGRP-4-specific siRNAs also dampened experimental arthritis in rats.
Conclusion. RasGRP-4 is aberrantly expressed in FLS and helps regulate their growth. This intracellular signaling protein is therefore a candidate target for dampening proliferative synovitis and joint destruction.

[Clinical significance of antiphospholipid antibody measured by EliA anticardiolipin antibodies and anti-β2Glycoprotein I antibodies in antiphospholipid syndrome].
Fujieda Y, Shida H, Oku K, Bohgaki T, Amengual O, Horita T, Yasuda S, Atsumi T
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 37, 5, 430, 436, Japan Society for Clinical Immunology, 2015年01月06日, ［査読有り］
日本語, Anticardiolipin antibodies (aCL-IgG/IgM) and anti-β2-glycoprotein I antibodies (aβ2GPI-IgG/IgM) are laboratory tests included in the current classification criteria for definite antiphospholipid syndrome (APS). However, not all of these assays have been commercially available in Japan. We investigated the efficacy of aCL-IgG/IgM and aβ2GPI-IgG/IgM assays using fluorescence enzyme immunoassay (Phadia:EliATM) for the diagnosis of APS in Japan. This study comprised 229 sera from patients (100 with APS and 129 without APS). The diagnosis of APS was made according to Sydney revised Sapporo criteria. EliATMCardiolipin and EliATMβ2-Glycoprotein (Phadia AB. Uppsala Sweden) were used to detect aCL IgG/M and aβ2GPI IgG/M, respectively. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were as follows
aCL-IgG (45%, 94%, 0.80), aCL-IgM (20%, 94%, 0.54), aβ2GPI-IgG (33%, 98%, 0.88) and aβ2GPI-IgM (16%, 99%, 0.64) respectively. aCL-IgM, aβ2GPI-IgG or aβ2GPI-IgM were detected in 10 patients (18%) with aCL-IgG negative. The use of Phadia:EliATMantiphospholipid antibodies assays improve the diagnostic yield of thrombotic risk in APS patients.

The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis/dermatomyositis
T. Kurita, S. Yasuda, O. Amengual, T. Atsumi
LUPUS, 24, 1, 3, 9, SAGE PUBLICATIONS LTD, 2015年01月, ［査読有り］
英語, Interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM) is often resistant to treatment and life threatening, being recognized as one of the severest complication in these autoimmune disorders. Patients with clinically amyopathic dermatomyositis (CADM) or those with anti-CADM140/MDA5 antibody are especially prone to develop rapidly progressive interstitial pneumonia. We retrospectively analyzed 46 patients with PM/DM admitted to our hospital and identified DM, rapidly progressive disease, honeycomb lung, CADM and extensive ILD as risk factors for recurrence or death. In the presence of two or more risk factors, the sensitivity and specificity for the prediction of death or relapse were 81.3% and 76.7%, respectively. Calcineurin inhibitors have been widely used as induction and maintenance therapy for PM/DM-associated ILD. Recently we reported the benefit of tacrolimus on the disease-free survival and event-free survival of the patients with PM/DM-associated ILD. Among those patients treated with tacrolimus, poor prognostic factors for death, recurrence or severe adverse event were identified as acute progression of the disease, honeycomb lung, forced vital capacity (FVC) less than 80% and having DM. The potential effectiveness of an intensive therapy protocol with triple therapy that comprises high-dose corticosteroids, calcineurin inhibitors and cyclophosphamide has been reported.

The participations of the physicians on the diagnosis and treatments of antiphospholipid related pregnancy morbidities in Japan: from the result of nationwide survey.
Oku K, Murashima A, Oomura K, Amengual O, Bohgaki T, Horita T, Yasuda S, Kaneko K, Nakanishi I, Nozawa K, Sugiura-Ogasawara M, Atsumi T
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 38, 6, 457, 465, 2015年, ［査読有り］

The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis.
Takashi Kurita, Shinsuke Yasuda, Koji Oba, Toshio Odani, Michihito Kono, Kotaro Otomo, Yuichiro Fujieda, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Tatsuya Atsumi
Rheumatology (Oxford, England), 54, 1, 39, 44, 2015年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Interstitial lung diseases (ILDs) complicated with PM or DM are frequently aggressive and refractory to treatment. Recently some reports have suggested the potential benefit of tacrolimus for severe ILD complicated with PM/DM. However, little evidence has yet shown the efficacy of tacrolimus in these settings. The aim of this study was to evaluate the efficacy of tacrolimus as a treatment for PM-/DM-related ILD. METHODS: This retrospective study comprised 49 previously untreated patients diagnosed as PM-/DM-related ILD admitted to Hokkaido University Hospital from January 2000 to July 2013. These patients were treated with tacrolimus plus conventional therapy or only with conventional therapy (prednisolone, i.v. CYC and/or ciclosporin). The primary endpoint was defined as the time to relapse or death of respiratory cause or a serious adverse event. The secondary endpoint was defined as the time from the initiation of immunosuppressive treatment to relapse or death of respiratory cause. Endpoints were compared by adjusted Cox regression model by using inverse probability of treatment weighting in order to reduce the impact of these selection biases and potential confounding factors. RESULTS: After adjustment, the tacrolimus group (n = 25) had significantly longer event-free survival as compared with the conventional therapy group (n = 24). The weighted hazard ratio (HR) was 0.32 (95% CI 0.14, 0.75, P = 0.008). In addition, the tacrolimus group had significantly longer disease-free survival as compared with the conventional therapy group. The weighted HR was 0.25 (95% CI 0.10, 0.66, P = 0.005). CONCLUSION: The addition of tacrolimus to conventional therapy significantly improved the prognosis of patients with PM-/DM-related ILD.

The function and the significance of full-automated tests for detecting antiphospholipid antibodies.
Oku K, Amengual O, Hisada R, Oomura K, Nakagawa I, Watanabe T, Bohgaki T, Horita T, Yasuda S, Atsumi T
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 38, 3, 157, 163, 2015年, ［査読有り］
日本語

抗リン脂質抗体症候群におけるエリア-抗リン脂質抗体測定試薬の臨床的有用性
藤枝 雄一郎, 志田 玄貴, 奥 健志, 坊垣 暁之, Amengual Olga, 堀田 哲也, 保田 晋助, 渥美 達也
日本臨床免疫学会会誌, 37, 5, 430, 436, (一社)日本臨床免疫学会, 2014年10月
日本語, 抗カルジオリピン抗体(抗CL)-IgG/IgM,抗β2-グリコプロテインI(抗β2GPI)-IgG/IgMは抗リン脂質抗体症候群(APS)の診断基準で認められた臨床検査であるが,本邦では抗CL-IgMや抗β2GPI-IgG/IgMはルーチン検査として確立していない.抗CL-IgG/IgM,抗β2GPI-IgG/IgM測定キット(Phadia:EliATM)を用いることによるAPSの診断における本邦での有用性を検討した.229例(APS群100例,非APS群129例)の保存血清を用い,EliATM抗CL(CL-IgG,CL-IgM)およびEliATM抗β2GPI(β2-IgG,β2-IgM)を測定した.感度,特異度,ROC曲線下面積はそれぞれ抗CL-IgG(45%,94%,0.80),抗CL-IgM(20%,94%,0.54),抗β2-IgG(33%,98%,0.88),抗β2-IgM(16%,99%,0.64)であった.APS100例で抗CL-IgG陰性55例のうち,抗CL-IgM,抗β2-IgG,抗β2-IgMのいずれかが陽性である症例は10例であった.複数の抗リン脂質抗体検査を組み合わせることで,APS診断の感度向上が確認された.(著者抄録)

Efficacy of Tocilizumab in Patients with Rheumatoid Arthritis: Sequential Evaluation Using Whole-Body Magnetic Resonance Imaging.
Michihito Kono, Shinsuke Yasuda, Kazumasa Ohmura, Tomoko Fukui, Sanae Shimamura, Ikuma Nakagawa, Atsushi Noguchi, Haruki Shida, Toshiyuki Watanabe, Yuka Shimizu, Takashi Kurita, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Keita Sakamoto, Tamotsu Kamishima, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 66, S518, S518, WILEY-BLACKWELL, 2014年10月, ［査読有り］
英語

Antiphospholipid scoring: significance in diagnosis and prognosis
K. Oku, O. Amengual, T. Atsumi
LUPUS, 23, 12, 1269, 1272, SAGE PUBLICATIONS LTD, 2014年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Recently our group introduced the antiphospholipid score (aPL-S), a quantitative marker that represents aPL profile. We have validated its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis. The study comprised two independent sets of patients with autoimmune diseases. In the first set of patients (n=233), the aPL-S was established by analyzing aPL profiles. In the second set of patients (n=411), the predictive value of the aPL-S for thrombosis was evaluated. To define aPL-S, we calculated the relative risks (approximated by odds ratios (ORs)) of having APS manifestations (thrombosis and/or pregnancy morbidity) for each of the aPL tests and devised an original formula in which aPL-S was determined by OR: aPL-S=5xexp ([OR] -5)/4. The receiver operating characteristic (ROC) curve showed a hyperbolic pattern and the area under the ROC curve value was 0.752 (0.686 for revised Sapporo criteria), implying that aPL-S is a potential quantitative marker for APS diagnosis. The OR for thrombosis in patients with a high aPL-S (30) was 5.27 (95% confidence interval (95% CI) 2.32-11.95, p<0.0001). By multivariate analysis, an aPL-S of 30 appeared to be an independent risk factor for thrombosis (hazard ratio 3.144 (95% CI 1.383-7.150), p=0.006). The aPL-S is a useful quantitative index for diagnosing APS and may be a predictive marker for thrombosis in autoimmune diseases.

Upregulation of Myxovirus Resistance Protein 1 in Patients with Neuropsychiatric Systemic Lupus Erythematosus
Yuka Shimizu, Shinsuke Yasuda, Takashi Kurita, Sanae Shimamura, Ikuma Nakagawa, Atsushi Noguchi, Haruki Shida, Toshiyuki Watanabe, Michihito Kono, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 66, S718, S719, WILEY-BLACKWELL, 2014年10月, ［査読有り］
英語

Antiphospholipid-Associated Nephropathy Is a Risk for Developing Arterial Thromboses in Patients with Systemic Lupus Erythematosus
Tomoko Fukui, Shinsuke Yasuda, Toshiyuki Watanabe, Kazumasa Ohmura, Sanae Shimamura, Ikuma Nakagawa, Atsushi Noguchi, Haruki Shida, Yuka Shimizu, Michihito Kono, Takashi Kurita, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 66, S3, S3, WILEY-BLACKWELL, 2014年10月, ［査読有り］
英語

The Protective Effects of Statins for Thrombosis in Patients with Systemic Lupus Erythematosus Positive for Antiphospholipid Antibodies.
Toshiyuki Watanabe, Kenji Oku, Olga Amengual, Eri Sugawara, Ryo Hisada, Kazumasa Ohmura, Tomoko Fukui, Sanae Shimamura, Ikuma Nakagawa, Atsushi Noguchi, Haruki Shida, Michihito Kono, Yuka Shimizu, Takashi Kurita, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 66, S1154, S1155, WILEY-BLACKWELL, 2014年10月, ［査読有り］
英語

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies
Olga Amengual, Tetsuya Horita, Walter Binder, Gary L. Norman, Zakera Shums, Masaru Kato, Kotaro Otomo, Yuichiro Fujieda, Kenji Oku, Toshiyuki Bohgaki, Shinsuke Yasuda, Tatsuya Atsumi
RHEUMATOLOGY INTERNATIONAL, 34, 9, 1225, 1230, SPRINGER HEIDELBERG, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite (TM) aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite (TM) aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen kappa = 0.962) and moderate agreement between the IgM aPS/PT assays (kappa = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.

14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends
Maria Laura Bertolaccini, Olga Amengual, Laura Andreoli, Tatsuya Atsumi, Cecilia B. Chighizola, Ricardo Forastiero, Philip De Groot, Gabriella Lakos, Marc Lambert, Pierluigi Meroni, Thomas L. Ortel, Michelle Petri, Anisur Rahman, Robert Roubey, Savino Sciascia, Melissa Snyder, Anne E. Tebo, Angela Tincani, Rohan Willis
AUTOIMMUNITY REVIEWS, 13, 9, 917, 930, ELSEVIER SCIENCE BV, 2014年09月, ［査読有り］
英語, Current classification criteria for definite Antiphospholipid Syndrome CAPS) require the use of three laboratory assays to detect antiphospholipid antibodies (aCL, anti-beta 2GPI and LA) in the presence of at least one of the two major clinical manifestations (i.e. thrombosis or pregnancy morbidity) of the syndrome. However, several other autoantibodies shown to be directed to other proteins or their complex with phospholipids have been proposed to be relevant to APS but their clinical utility and their diagnostic value remains elusive.
This report summarizes the findings, conclusions and recommendations of the "APS Task Force 3-Laboratory Diagnostics and Trends" meeting that took place during the 14th International Congress on Antiphospholipid Antibodies (APLA 2013, September 18-21, Rio de Janeiro, Rj, Brazil). (c) 2014 Elsevier B.V. All rights reserved.

Essential role of the p38 mitogen-activated protein kinase pathway in tissue factor gene expression mediated by the phosphatidylserine-dependent antiprothrombin antibody
Kenji Oku, Olga Amengual, Polona Zigon, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi
RHEUMATOLOGY, 52, 10, 1775, 1784, OXFORD UNIV PRESS, 2013年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. The aim of this study was to investigate the effects of phosphatidylserine-dependent antiprothrombin antibody (aPS/PT) on the expression of tissue factor (TF) and the signal transduction pathway in procoagulant cells.
Methods. Peripheral blood mononuclear cells (PBMCs) from a healthy donor, murine monocyte RAW264.7 cells and human umbilical vein endothelial cells (HUVECs) were treated with either IgG fractions obtained from APS patients who were positive for aPS/PT or a murine monoclonal aPS/PT antibody, 231D, in the presence of prothrombin. The levels of TF mRNA were measured using real-time PCR. TF function, as measured by procoagulant activity, was determined with a clotting assay. 231D binding on the surface of treated cells was determined by flow cytometric analysis. Screening for phosphorylation of intracellular signalling proteins was conducted using an array assay. Phosphorylation of p38 MAPK was quantitatively analysed with ELISA, and SB203580 was used as a specific inhibitor of p38 MAPK. Specific siRNA for p38 MAPK was used for the knockdown assay.
Results. The IgG fractions from APS patients and 231D induced TF mRNA overexpression and shortening of coagulation time in cells in the presence of prothrombin. The 231D moiety induced phosphorylation of p38 MAPK after binding to the cell surface of RAW264.7 cells. SB203580 or p38 siRNA significantly hampered TF overexpression.
Conclusion. Expression of TF in procoagulant cells was induced by aPS/PT via p38MAPK phosphorylation. This phenomenon may be correlated with the thrombogenicity of APS.

Autoantibodies Against Component Of Complement One Contribute To The Complement Activation and Clinical Manifestation Of Antiphospholipid Syndrome (APS) Especially In Refractory Cases
Oku Kenji, Amengual Olga, Nakagawa Ikuma, Watanabe Toshiyuki, Kanetsuka Yusaku, Bohgaki Toshiyuki, Horita Tetsuya, Yasuda Shinsuke, Atsumi Tatsuya
ARTHRITIS AND RHEUMATISM, 65, S7, S8, 2013年10月, ［査読有り］

Decreased Levels Of Splicing Factor 2/Alternative Splicing Factor (SF2/ASF) Correlate With Lower Transcript Levels Of The RasGRP1 Normal Isoform In Lupus T Cells.
Kurita Takashi, Yasuda Shinsuke, Moulton Vaishali R, Kono Michihito, Koide Hideyuki, Oku Kenji, Bohgaki Toshiyuki, Amengual Olga, Horita Tetsuya, Tsokos George C, Atsumi Tatsuya
ARTHRITIS AND RHEUMATISM, 65, S691, 2013年10月, ［査読有り］

The involvement of CD36 in monocyte activation by antiphospholipid antibodies
M. Kato, T. Atsumi, K. Oku, O. Amengual, H. Nakagawa, Y. Fujieda, K. Otomo, T. Horita, S. Yasuda, T. Koike
Lupus, 22, 8, 761, 771, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: CD36, known as a scavenger receptor, is a transmembrane glycoprotein expressed on monocytes, platelets and endothelial cells, recognizes multiple ligands, including phosphatidylserine, and regulates atherogenesis and thrombosis. The objective of this study is to investigate the possible involvement of CD36 in the pathophysiology of thrombosis in patients with antiphospholipid syndrome (APS). Methods: First, rs3765187, a missense mutation linked to CD36 deficiency, was investigated by TaqMan polymerase chain reaction (PCR) genotyping method in 819 Japanese, including 132 patients with APS, 265 with systemic lupus erythematosus (SLE) in the absence of APS, and 422 healthy subjects. Then, the involvement of CD36 in antiphospholipid antibody (aPL)-induced tissue factor (TF) expression was examined using CD36-null mice or anti-CD36. Purified IgG from patients with APS and a monoclonal phosphatidylserine-dependent antiprothrombin antibody were used in these experiments. TF expression was tested by real-time PCR and flow cytometry. Results: Minor allele carrier of rs3765187 was less frequent in patients with APS (3.8% p=0.032), but not in patients with SLE in the absence of APS (7.9% p=0.32), compared with healthy subjects (10.2%). The aPL-induced TF expression was significantly suppressed on peritoneal macrophages from CD36-null mice compared to wild type and significantly inhibited by anti- CD36 on human monocytes. Conclusions: The gene mutation linked to CD36 deficiency was less frequent in patients with APS. The deficient or suppressed CD36 function significantly reduced aPL-induced TF expression in vitro. Taken together, in a susceptible background CD36 scavenger receptor function may be involved in the thrombotic pathophysiology in patients with APS. © The Author(s), 2013. Reprints and permissions.

Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome
Olga Amengual, Tatsuya Atsumi, Kenji Oku, Eriko Suzuki, Tetsuya Horita, Shinsuke Yasuda, Takao Koike
Modern Rheumatology, 23, 1, 81, 88, 1, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: Thrombus formation is the key event of vascular manifestations in antiphospholipid syndrome (APS). Phosphatidylserine (PS) is normally sequestered in the inner leaflet of cell membranes. Externalization of PS occurs during cell activation and is essential for promoting blood coagulation and for the binding of antiphospholipid antibodies (aPL) to cells. One of the molecules involved in PS externalization is phospholipid scramblase 1 (PLSCR1). We evaluated PLSCR1 expression on monocytes from APS patients and analyzed the in vitro effect of monoclonal aPL on PLSCR1 expression. Patients and methods: Forty patients with APS were investigated. In vitro experiments were performed in monocyte cell lines incubated with monoclonal aPL. PLSCR1 expression was determined by quantitative real-time polymerase chain reactions. PS exposure on CD14+ cell surface was analyzed by flow cytometry. Results: Levels of full-length PLSCR1 messenger RNA (mRNA) were significantly increased in APS patients compared with healthy controls (2.4 ± 1.2 vs. 1.3 ± 0.4, respectively, p <
0.001). In cultured monocytes, interferon alpha enhanced tissue-factor expression mediated by β2-glycoprotein-I-dependent monoclonal anticardiolipin antibody. Conclusions: Monocytes in APS patients had increased PLSCR1 mRNA expression. © 2012 Japan College of Rheumatology.

Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid syndrome
Y. Fujieda, T. Atsumi, O. Amengual, T. Odani, K. Otomo, M. Kato, K. Oku, Y. Kon, T. Horita, S. Yasuda, T. Koike
LUPUS, 21, 14, 1506, 1514, SAGE PUBLICATIONS LTD, 2012年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To study the clinical and immunological manifestations of antiphospholipid syndrome (APS) in the Japanese population by a single-centre registration. Methods: In this retrospective cohort study, 141 consecutive patients with APS, fulfilling the Sydney revised Sapporo criteria for definite APS, who visited our autoimmune clinic from 1988 to 2010, were recruited and followed up. All the patients were interviewed and underwent a general physical examination by qualified rheumatologists on the day of blood sampling. Results: The population comprised 119 woman and 22 men with a mean age at diagnosis of 44 years (range 9-79 years). Seventy patients (49.6%) had primary APS, and 71 (50.4%) had systemic lupus erythematosus. The prevalence of thrombosis was 85.8 per cent, arterial thrombosis was found in 93 patients (66.0%) and venous thrombosis was found in 46 patients (32.6%). The most common thrombosis was cerebral infarction [86/141 (61.0%)] followed by deep vein thrombosis [33/141 (23.4%)]. Among 70 pregnant women, 45 (64.3%) had obstetric complications. Lupus anticoagulant was detected in 116 patients (82.3%), anticardiolipin antibodies in 83 (58.9%), anti-beta 2 glycoprotein I antibodies in 73 (51.8%) and phosphatidylserine-dependent antiprothrombin antibodies in 98 (69.5%). Conclusion: High prevalence of arterial thrombosis was noted in Japanese patients with APS. The profile of heterogeneous and complex clinical manifestations was substantiated in Japanese patients with APS. Lupus (2012) 21, 1506-1514.

Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome
Kenji Oku, Olga Amengual, Tatsuya Atsumi
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 42, 10, 1126, 1135, WILEY-BLACKWELL, 2012年10月, ［査読有り］
英語, Eur J Clin Invest 2012; 42 (10): 11261135 Abstract In patients with the antiphospholipid syndrome (APS), the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes arteriovenous thrombosis and pregnancy complications. To date, the pathogenicity of the antiphospholipid antibodies has been the focus of analysis. Recently, the antibodies were reported to be capable of direct cell activation, and research on the underlying mechanism is ongoing. The antiphospholipid antibodies bind to the membranes of vascular endothelial cells, monocytes and platelets, provoking tissue factor expression and platelet aggregation. This activation functions as intracellular signalling, independent of the cell type, to activate p38MAPK and the transcription factor NF?B. Currently, there are multiple candidates for the membrane receptors of the antiphospholipid antibodies that are being tested for potential in specific therapy. Recently, APS was reported to have significant comorbidity with complement activation, and it was proposed that this results in placental damage and cell activation and, therefore, could be the primary factor for the onset of pregnancy complications and thrombosis. The detailed mechanism of complement activation remains unknown; however, an inflammation-inducing substance called anaphylatoxin, which appears during the activation process of the classical complement pathway, is thought to be a key molecule. Complement activation occurs in tandem, regardless of the pathology of APS or the type of antiphospholipid antibody, and it is thought that this completely new understanding of the mechanism will contribute greatly to comprehension of the pathology of APS.

Ribophorin II Is Involved in the Tissue Factor Expression Mediated by Phosphatidylserine-Dependent Antiprothrombin Antibody On Monocytes.
Fujieda Yuichiro, Amengual Olga, Kanetsuka Yusaku, Odani Toshio, Otomo Kotaro, Oku Kenji, Bohgaki Toshiyuki, Horita Tetsuya, Yasuda Shinsuke, Kuroki Kimiko, Maenaka Katsumi, Matsumoto Masaki, Hatakeyama Shigetsugu, Atsumi Tatsuya
ARTHRITIS AND RHEUMATISM, 64, 10, S741, 2012年10月, ［査読有り］

Dual Antiplatelet Therapy As Prophylaxis of Recurrent Arterial Thrombosis in Patients with antiphospholipid Syndrome.
Fujieda Yuichiro, Amengual Olga, Watanabe Toshiyuki, Kono Michihito, Kanetsuka Yusaku, Kurita Takashi, Odani Toshio, Otomo Kotaro, Bohgaki Toshiyuki, Horita Tetsuya, Yasuda Shinsuke, Atsumi Tatsuya
ARTHRITIS AND RHEUMATISM, 64, 10, S1036, 2012年10月, ［査読有り］

Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events
Kotaro Otomo, Tatsuya Atsumi, Olga Amengual, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Tetsuya Horita, Shinsuke Yasuda, Takao Koike
ARTHRITIS AND RHEUMATISM, 64, 2, 504, 512, WILEY-BLACKWELL, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective To define the antiphospholipid score (aPL-S) by testing multiple antiphospholipid antibodies (aPL) and to evaluate its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis.
Methods. This study comprised 2 independent sets of patients with autoimmune diseases. In the first set of patients (n = 233), the aPL profiles were analyzed. Five clotting assays for testing lupus anticoagulant and 6 enzyme-linked immunosorbent assays (IgG/IgM anticardiolipin antibodies, IgG/IgM anti-beta(2)-glycoprotein I, and IgG/IgM phosphatidylserine-dependent antiprothrombin antibodies) were included. The association of the aPL-S with a history of thrombosis/ pregnancy morbidity was assessed. In the second set of patients (n = 411), the predictive value of the aPL-S for thrombosis was evaluated retrospectively. Two hundred ninety-six of these patients were followed up for > 2 years. The relationship between the aPL-S and the risk of developing thrombosis was analyzed.
Results. In the first set of patients, the aPL-S was higher in those with thrombosis/pregnancy morbidity than in those without manifestations of APS (P < 0.00001). For the aPL-S, the area under the receiver operating characteristic curve value was 0.752. In the second set of patients, new thromboses developed in 32 patients. The odds ratio (OR) for thrombosis in patients with an aPL-S of > 30 was 5.27 (95% confidence interval [ 95% CI] 2.32-11.95, P < 0.0001). By multivariate analysis, an aPL-S of > 30 appeared to be an independent risk factor for thrombosis (hazard ratio 3.144 [ 95% CI 1.383-7.150], P = 0.006).
Conclusion. The aPL-S is a useful quantitative index for diagnosing APS and may be a predictive marker for thrombosis in autoimmune diseases.

Role of Apolipoprotein B100 and Oxidized Low-Density Lipoprotein in Anti-beta2 Glycoprotein I Induced Tissue Factor Expression on Monocytes
Otomo Kotaro, Atsumi Tatsuya, Fujieda Yuichiro, Nakagawa Hisako, Kato Masaru, Amengual Olga, Horita Tetsuya, Yasuda Shinsuke, Matsumoto Masaki, Hatakeyama Shigetsugu, Koike Takao
ARTHRITIS AND RHEUMATISM, 63, 10, S6, 2011年10月, ［査読有り］

Pathophysiology of Thrombosis and Potential Targeted Therapies in Antiphospholipid Syndrome
Olga Amengual, Tatsuya Atsumi, Takao Koike
CURRENT VASCULAR PHARMACOLOGY, 9, 5, 606, 618, BENTHAM SCIENCE PUBL LTD, 2011年09月, ［査読有り］
英語, 研究論文（学術雑誌）, The antiphospholipid syndrome (APS) is an autoimmune disease in which recurrent vascular thrombosis, pregnancy morbidity or a combination of these events is associated with the persistent presence of circulating antiphospholipid antibodies (aPL). Evidence shows that the dominant antigenic targets for aPL in APS are phospholipid-binding plasma proteins such as beta 2glycoprotein I and prothrombin.
The pathogenic role of aPL in thrombosis is widely accepted but the mechanisms by which these antibodies mediate disease are only partially understood. aPL may affect the normal procoagulant and anticoagulant reactions occurring on cell surface, and also may interact with certain cells, altering the expression and secretion of procoagulant substances.
The intracellular signal transduction triggered by aPL has been a focus of intensive research and the p38 mitogen activated protein kinase (MAPK) pathway has been revealed as a major player in the aPL-mediated cell activation. In addition, some candidates as cell-receptor for phospholipid-binding plasma proteins have been identified. The recognition of the intracellular signaling triggered by aPL is a step forward in the design of new modalities of targeted therapies for thrombosis in APS including specific inhibitors of MAPK pathway or antagonists of the putative receptors. Furthermore, novel findings regarding the role of aPL in T-cells responses mark new advances in the understanding of the immunological reactions in APS and open new insights into possible therapeutic approaches to APS.
In this article, we review the pathophysiological mechanisms of thrombosis and the specific new targeted therapies for the treatment in APS.

世界のリウマチガイドラインをみわたす ３）各国の治療ガイドライン ｢欧州各国の抗TNF薬使用のためのリコメンデーション｣.　　　　　　　　　　　　　　　
アメングアル オルガ
分子リウマチ治療, 4, 4, 16, 20, 2011年, ［査読有り］
日本語

Non-Criteria” aPL tests: report of a task force and preconference workshop at the 13th International Congress on Antiphospholipid Antibodies
Maria Laura. Bertolaccini, Olga. Amengual, Tatsuya. Atsumi, Walter L. Binder, William H. Kutteh, Bas De Laat, Ricardo Forastiero, Marc Lambert, Hidehiko Matsubayashi, Vijaya L. Murthy, Michelle Petri, Jacob H. Rand, Marielle Sanmarco, Anne E. Tebo, Silvia S. Pierangeli
Lupus, 20, 2, 191, 205, Springer US, 2011年01月01日, ［査読有り］
英語, 論文集(書籍)内論文, Current classification criteria for antiphospholipid syndrome (APS) recommend the use of one or more of three positive standardized laboratory assays to detect antiphospholipid antibodies (aPL) in the presence of at least one of the two major clinical manifestations (i.e., thrombosis or pregnancy morbidity). However, several other autoantibodies shown to be directed against phospholipids other than cardiolipin and/or their complexes with proteins of the coagulation cascade have also been proposed to be important in APS. This chapter summarizes the recommendations of a Task Force of worldwide scientists who discussed and analyzed critical questions related to “noncriteria” aPL tests in an evidence-based manner, during the 13th International Congress on Antiphospholipid Antibodies (APLA 2010, April 13–16, 2010, Galveston, TX).

Increased Expression of Phospholipid Scramblase 1 in Monocytes from Patients with Systemic Lupus Erythematosus
Eriko Suzuki, Olga Amengual, Tatsuya Atsumi, Kenji Oku, Toko Hashimoto, Hiroshi Kataoka, Tetsuya Horita, Shinsuke Yasuda, Masahiro Ieko, Kazuaki Fukushima, Takao Koike
JOURNAL OF RHEUMATOLOGY, 37, 8, 1639, 1645, J RHEUMATOL PUBL CO, 2010年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. A high incidence of thromboembolic events has been reported in patients with systemic lupus erythematosus (SLE). Phosphatidylserine (PS) is normally sequestered in the inner leaflet of cell membranes. Externalization of PS during cell activation is mediated by phospholipid scramblase 1 (PLSCR1) and has a central role in promoting blood coagulation. We investigated the underlying pathogenic status of thrombophilia in SLE by analyzing PLSCR1 expression on monocytes from patients with SLE.
Methods. Sixty patients with SLE were evaluated. Twenty-three patients had antiphospholipid syndrome (APS/SLE). Plasma D-dimer levels were measured as a marker of fibrin turnover. The cDNA encoding human PLSCR1 was cloned from the total RNA extract from monocytes, and independent clones were sequenced. PLSCR1 mRNA expression in CD14+ cells was determined by real-time polymerase chain reaction. PS exposure on CD14+ cell surface was analyzed by flow cytometry.
Results. Elevated D-dimer levels were found in plasma from SLE patients. Three splice variants of PLSCR1 mRNA were identified in all subjects, and levels of full-length PLSCR1 mRNA were significantly increased in SLE compared to healthy controls (2.9 +/- 1.5 vs 1.3 +/- 0.4, respectively; p < 0.0001). Flow-cytometry analysis showed relative enhancement of PS exposure in the surface of CD14+ cells in SLE patients compared to healthy controls.
Conclusion. Novel PLSCR1 splice variants were identified. Monocytes in SLE patients had enhanced PLSCR1 mRNA expression, as well as increased fibrin turnover and cell-surface PS exposure, indicating that PLSCR1 may, in part, contribute to the prothrombotic tendency in SLE. (First Release June 1 2010; J Rheumatol 2010;37:1639-45; doi:10.3899/jrheum.091420)

Anti-beta 2 glycoprotein-I antibody increases the risk of pregnancy-induced hypertension: a case-controlled study
Hideto Yamada, Tatsuya Atsumi, Olga Amengual, Takao Koike, Itsuko Furuta, Kaori Ohta, Gen Kobashi
JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 84, 1, 95, 99, ELSEVIER IRELAND LTD, 2010年01月, ［査読有り］
英語, 研究論文（学術雑誌）, The aim of this study was to evaluate whether anti-beta 2 glycoprotein-I antibody (anti-beta 2GPI) of the IgG or IgM classes is associated with the development of pregnancy-induced hypertension (PIH) or preeclampsia in the Japanese population. In a case-controlled cohort study, peripheral blood was obtained at 8-14 weeks of gestation from a consecutive series of 1155 women. The case group comprised 36 patients who later developed PIH during the pregnancy. Of the 36 PIH patients, 13 had severe PIH, 18 had preeclampsia and 11 had severe preeclampsia. One hundred and eleven age- and parity-matched women whose pregnancies ended in normal delivery without obstetric complications were selected as controls. We found that a titer of anti-beta 2GPI IgG >= 1.0 U/ml was a risk factor for severe PIH (P = 0.023, OR 5.7 95%CI 1.4-22.8). In addition, titers of anti-beta 2GPI IgM >= 1.2 U/ml was found to be a risk factor for PIH (P = 0.001, OR 8.8 95%CI 1.6-47.5). In women positive for anti-beta 2GPI but negative for lupus anticoagulant, anti-cardiolipin, phosphatidylserine-dependent anti-prothrombin, or kininogen-dependent anti-phosphatidylethanolamine antibodies, the presence of anti-beta 2GPI was not a significant risk factor for development of PIH or preeclampsia. In conclusion, the presence of anti-beta 2GPI antibody represents a risk factor for developing PIH and severe PIH. This finding Supports the utility of anti-beta 2GPI determination as one of the laboratory criteria for anti-phospholipid syndrome classification. The usefulness of anti-beta 2GPI measurement among women without other anti-phospholipid antibodies requires further study. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

The Effects of Phosphatidylserine-Dependent Antiprothrombin Antibody on Thrombin Generation
Yoshie Sakai, Tatsuya Atsumi, Masahiro Ieko, Olga Amengual, Shin Furukawa, Akira Furusaki, Miyuki Bohgaki, Hiroshi Kataoka, Tetsuya Horita, Shinsuke Yasuda, Takao Koike
ARTHRITIS AND RHEUMATISM, 60, 8, 2457, 2467, WILEY-LISS, 2009年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Antibodies to prothrombin (APTs) and to beta(2)-glycoprotein I are the major autoantibodies responsible for lupus anticoagulant (LAC) activity. APTs comprise antibodies against prothrombin alone as well as antibodies against phosphatidylserine/prothrombin complex (anti-PS/PT), the latter being highly associated with the anti phospholipid syndrome (APS). The effect of anti-PS/PT on thrombin generation has not been elucidated, and the paradoxical effect of LAC (an anticoagulant in vitro, but a procoagulant in vivo) remains an enigma. The purpose of this study was to investigate the effects of anti-PS/PT on thrombin generation and to examine the LAC paradox.
Methods. We evaluated 36 anti-PS/PT-positive APS patients and 127 healthy subjects. Markers of in vivo thrombin/fibrin generation, including prothrombin fragment F(1+2), thrombin-antithrombin III complex, soluble fibrin monomer, D-dimer, and fibrin degradation products, were measured. Mouse monoclonal anti-PS/PT antibody 231D was established, and its effects on in vitro thrombin generation were investigated by chromogenic assay.
Results. Significantly elevated levels of markers thrombin/fibrin generation were observed in anti-PS/PT-positive patients, regardless of the presence or absence of anticardiolipin antibodies, as compared with healthy subjects. In the presence of low concentrations of human activated factor V (FVa), monoclonal antibody 231D increased thrombin generation in a dose-dependent manner. In contrast, when high concentrations of FVa were added, monoclonal antibody 231D decreased thrombin generation. Under a constant concentration of FVa a high concentration of human FXa enhanced the effect of 231D.
Conclusion. The presence of anti-PS/PT greatly correlated with increased thrombin generation in APS patients. The in vitro effects of monoclonal antibody 231D on thrombin generation are "biaxial" according to the FVa/FXa balance. These data may serve as a clue to understanding the LAC paradox and the thrombogenic properties of anti-PS/PT.

Complement activation in patients with primary antiphospholipid syndrome
K. Oku, T. Atsumi, M. Bohgaki, O. Amengual, H. Kataoka, T. Horita, S. Yasuda, T. Koike
ANNALS OF THE RHEUMATIC DISEASES, 68, 6, 1030, 1035, B M J PUBLISHING GROUP, 2009年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To investigate the significance of complement activation in patients with primary antiphospholipid syndrome (APS).
Methods: Thirty-six patients with primary APS, 42 control patients with non-systemic lupus erythematosus (SLE) connective tissue diseases, and 36 healthy volunteers were analysed retrospectively. Serum complement levels (C3, C4, CH(50)) and anaphylatoxins (C3a, C4a, C5a) were examined in all subjects, and serum complement regulatory factors (factor H and factor I) were measured in patients with primary APS. Plasma anticoagulant activity was determined in a mixing test using the activated partial thromboplastin time.
Results: Serum complement levels were significantly lower in patients with primary APS than in patients with non-SLE connective tissue diseases ( mean (SD) C3: 81.07 (17.86) vs 109.80 (22.76) mg/dl, p<0.001; C4: 13.04 (8.49) vs 21.70 (6.96) mg/dl, p<0.001; CH(50): 31.32 (8.76) vs 41.40 (7.70) U/ml, p<0.001) or healthy volunteers. Only two healthy subjects with low serum C4 levels showed hypocomplementaemia, whereas most patients with primary APS showed raised serum C3a and C4a. No subjects showed raised C5a. Patients with primary APS with low serum C3 or C4 had significantly higher levels of C3a or C4a than healthy controls. No patients had low serum complement regulatory factors. Among patients with primary APS, hypocomplementaemia was significantly more common in those with high anticoagulant activity than in those with low or normal activity.
Conclusion: Hypocomplementaemia is common in patients with primary APS, reflecting complement activation and consumption, and was correlated with anticoagulant activity, suggesting that antiphospholipid antibodies may activate monocytes and macrophages via anaphylatoxins produced in complement activation.

ホスファチジルセリン依存性抗プロトロンビン抗体による向血栓細胞における組織因子発現機序　　　　　　　　　　　　　　　
奥 健志, 渥美 達也, Amengual Olga, 宮本 江里子, 藤枝 雄一郎, 大友 耕太郎, 加藤 将, 橋本 陶子, 片岡 浩, 堀田 哲也, 保田 晋助, 小池 隆夫
日本臨床分子医学会学術総会プログラム・抄録集, 46回, 77, 77, 日本臨床分子医学会, 2009年04月
日本語

原発性抗リン脂質抗体症候群における低補体血症の意義　　　　　　　　　　　　　　　
奥 健志, 渥美 達也, オルガ・アメングアル, 藤枝 雄一郎, 大友 耕太郎, 加藤 将, 橋本 陶子, 片岡 浩, 堀田 哲也, 保田 晋助, 小池 隆夫
日本血栓止血学会誌, 20, 2, 230, 230, (一社)日本血栓止血学会, 2009年04月
日本語

The phosphatidylserine-dependent monoclonal antiprothrombin antibody with lupus anticoagulant activity induces tissue factor and adhesion molecules expression on endothelial cells: Possible implication of p38 mitogen-activate protein kinase (MAPK) pathway
Oku Kenji, Atsumi Tatsuya, Amengual Olga, Miyamoto Eriko, Otomo Kotaro, Kato Masaru, Kataoka Hiroshi, Horita Tetsuya, Yasuda Shinsuke, Koike Takao
ARTHRITIS AND RHEUMATISM, 58, 9, S404, S405, 2008年09月, ［査読有り］

Antiprothrombin antibody testing: Detection and clinical utility
Kenji Oku, Tatsuya Atsumi, Olga Amengual, Takao Koike
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 34, 4, 335, 339, THIEME MEDICAL PUBL INC, 2008年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Anticardiolipin antibody (aCL), anti-beta 2 glycoprotein I antibodies, and lupus anticoagulant (LA) are the only laboratory tests considered within the revised criteria for the classification of the antiphospholipid syndrome (APS). Recently, antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have been detected, and these antibodies, rather than antibodies against prothrombin alone, are closely associated with APS and LA. The sensitivity and specificity of aPS/PT for the diagnosis of APS were assessed in a population of patients with a variety of autoimmune disorders. aCL and aPS/PT have similar diagnostic value for APS, therefore aPS/PT should be further explored, not only for research purposes but also as a candidate for one of the laboratory criteria for the classification of the APS.

抗リン脂質抗体症候群(APS)患者単球におけるPhospholipid Scramblase1(PLSCR1)の発現　　　　　　　　　　　　　　　
宮本 江里子, 渥美 達也, オルガ・アメングアル, 奥 健志, 大友 耕太郎, 加藤 将, 片岡 浩, 堀田 哲也, 保田 晋助, 小池 隆夫
日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 52回・17回, 311, 311, (一社)日本リウマチ学会, 2008年04月
日本語

Antiphospholipid antibodies and the antiphospholipid syndrome　　　　　　　　　　　　　　　
Olga Amengual, Tatsuya Atsumi, Takao Koike
New Immunology Research Developments, 303, 332, Nova Science Publishers, Inc., 2008年01月01日
英語, 論文集(書籍)内論文, The association of persistent presence of circulating antiphospholipid antibodies (aPL) and recurrent vascular thrombosis, pregnancy morbidity or a combination of these events is termed antiphospholipid syndrome (APS). The dominant antigenic targets in APS are phospholipid (PL)-binding plasma proteins such as ß2glycoprotein I (ß2GPI) and prothrombin. In the last few years, great interest has arisen concerning the binding of aPL to endothelial cells or other pro-coagulant cells, and how this binding mediates cell dysfunctions that potentially induce the clinical manifestations of APS. Pro-coagulant cells, exposed by aPL in the presence of PL -binding proteins, produce thrombophilic molecules such as tissue factor, adhesion molecules and tumor necrosis factor a. It is now recognized that the p38 mitogen activated protein kinase (MAPK) pathway plays an important role in aPL-mediated cell activation. Moreover, the role of annexin II as receptor for ß2GPI and the interaction of ß2GPI with different members of the low density lipoprotein receptor family have been reported. In this chapter we review the new research relating to the pathophysiological mechanisms that may contribute to the manifestations of APS, focusing on the procoagulant cell scenario.

Thrombotic microangiopathy in patients with phosphatidylserine dependent antiprothrombin antibodies and antiphospholipid syndrome
Y. Kon, T. Atsumi, H. Hagiwara, A. Furusaki, H. Kataoka, T. Horita, S. Yasuda, O. Amengual, K. Takao
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 26, 1, 129, 132, CLINICAL & EXPER RHEUMATOLOGY, 2008年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Thrombotic microangiopathy (TMA) is a rare disorder characterized by microvascular thrombosis. TMA has been reported in patients with antiphospholipid antibodies and/or antiphospholipid syndrome but its pathogenesis is not clarified. We present two patients with TMA associated with IgG phosphatidylserine dependent antiprothrombin antibodies (aPS/P7).
Case 1: A 44-year-old Japanese female with systemic lupus erythematosus (SLE) and positive lupus anticoagulant (LA) was started on ticlopidine after having stroke. Four weeks later she developed MA. IgG/MIA anticardiolipin antibodies (aCL) were negative, but strong positive IgG aPS/PT were detected.
Case 2: A 32-year-old Russian female with SLE was admitted because of hypertension, renal insufficiency and proteinuria at 14 weeks of pregnancy. She developed TMA after surgical abortion. IgG aPS/PT and LA were strongly positive but IgG/MIA aCL were negative. Neither case had von Willebrand factor cleaving protease (ADAMTS-13), suggesting that TMA in those patients was associated with thrombophilia rather than insufficient ADAMTS-13. Both patients were successfully treated with a series of plasma exchange.

A polymorphism in human platelet antigen 6b and risk of thrombocytopenia in patients with systemic lupus erythematosus
Olga Amengual, Tatsuya Atsumi, Yukiko Komano, Hiroshi Kataoka, Tetsuya Horita, Shinsuke Yasuda, Takao Koike
ARTHRITIS AND RHEUMATISM, 56, 8, 2803, 2805, WILEY-LISS, 2007年08月, ［査読有り］
英語

Antiphospholipid antibodies: Lessons from the bench
Takao Koike, Miyuki Bohgaki, Olga Amengual, Tatsuya Atsumi
JOURNAL OF AUTOIMMUNITY, 28, 2-3, 129, 133, ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 2007年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Antiphospholipid antibodies (aPL) are an heterogeneous group of circulating immunoglobulins arising in a wide range of infectious and autoimmune diseases. Since the early 80 s, the interest on anticardiolipin antibodies (aCL) has exponentially increased due to their association with thrombosis. The antiphospholipid syndrome (APS) was defined as a clinical disorder characterized by thrombosis and pregnancy morbidity associated to the persistent presence of aCL and/or lupus anticoagulant (LA). Thrombosis is the major manifestation in patients with aPL, but the spectrum of symptoms and signs associated with aPL has considerably broadened, and other manifestations such as thrombocytopenia, nonthrombotic neurological syndromes, psychiatric manifestations, livedo reticularis, skin ulcers, haemolytic anemia, pulmonary hypertension, cardiac valve abnormality and atherosclerosis have also been related to the presence of those antibodies. Numerous mechanisms have been proposed to explain the thrombotic tendency of patients with aPL, but the pathogenesis seems to be multifactorial. (C) 2007 Elsevier Ltd. All rights reserved.

Pathophysiology of the antiphospholipid syndrome: Roles of anticardiolipin antibodies in thrombosis and fibrinolysis
Olga Amengual, Tatsuya Atsumi, Takao Koike
APLAR Journal of Rheumatology, 9, 4, 377, 386, 2006年12月, ［査読有り］, ［招待有り］
英語, 研究論文（学術雑誌）, Antiphospholipid antibodies (aPL) (anticardiolipin antibodies and lupus anticoagulant) are associated with thrombosis and pregnancy morbidity, the antiphospholipid syndrome (APS). Despite the clear association between aPL and those manifestations, the precise underlying disease mechanisms remain unclear. APL may affect the normal procoagulant and anticoagulant reactions occurring on cell membranes, and also may interact with certain cells, altering the expression and secretion of procoagulant substances. In this article, we review the immunological characteristics of anticardiolipin antibodies and their potential effects on the coagulation and fibrinolytic systems implicated in the development of thrombotic complications in patients with APS. © 2006 Asia Pacific League of Associations for Rheumatology.

Beta2glycoprotein I-Dependent anticardiolipin antibodies-induced tissue factor expression is enhanced by interferon alpha; A crucial role for lipid scramblase 1.
Amengual Olga, Atsumi Tatsuya, Kataoka Hiroshi, Horita Tetsuya, Yasuda Shinsuke, Koike Takao
ARTHRITIS AND RHEUMATISM, 54, 9, S560, 2006年09月, ［査読有り］

Protective effect of pravastatin on vascular endothelium in patients with systemic sclerosis: a pilot study
S. Furukawa, S. Yasuda, O. Amengual, T. Horita, T. Atsumi, T. Koike
ANNALS OF THE RHEUMATIC DISEASES, 65, 8, 1118, 1120, B M J PUBLISHING GROUP, 2006年08月, ［査読有り］
英語

Research around beta 2-glycoprotein I: A major target for antiphospholipid antibodies
T Atsumi, O Amengual, S Yasuda, E Matsuura, T Koike
AUTOIMMUNITY, 38, 5, 377, 381, TAYLOR & FRANCIS LTD, 2005年08月, ［査読有り］
英語, 研究論文（学術雑誌）, beta 2-Glycoprotein I (beta 2GPI), a phospholipid-binding protein, is one of the major target antigens for antiphospholipid antibodies (aPL) found in patients with antiphospholipid syndrome (APS). Thrombophilic disorders in APS patients are strongly associated with aPL, and their pathogenic properties depend on the presence of beta 2GPI. Procoagulant cell stimulation by aPL, via beta 2GPI, is one of the most plausible mechanisms of thrombosis in APS, and p38 mitogen activated protein kinase (MAPK) pathway plays a crucial role in such activation. beta 2GPI is proteolytically cleaved in domain V by activated factor X or plasmin, leading to the generation of the nicked form of beta 2GPI. Recently, increasing attention is focused on the role of nicked-beta 2GPI as a regulator of extrinsic fibrinolysis pathway.

Antiprothombin antibodies–are they worth assaying
Atsumi T, Amengual O, Yasuda S, Koike T
20th Congress of the International Society on Thrombosis and Haemostasis, Sydney, Australia, 114, 5-6, 533, 538, PERGAMON-ELSEVIER SCIENCE LTD, 2005年08月, ［査読有り］
英語, According to the preliminary classification criteria of the antiphospholipid syndrome (APS) (Sapporo Criteria), beta(2)-glycoprotein I (beta(2)GPI)-dependent anticardiolipin antibodies (aCL) and Lupus anticoagulant (LA) are the only laboratory tests considered as criteria for the classification of the APS. Recently, antibodies against phosphatidylserine-prothrombin complex (aPS/PT) have been detected and these antibodies, rather than antibodies against prothrombin alone, are closely associated with APS and LA. We assessed the sensitivity and specificity of aPS/PT for the diagnosis of APS in our population of patients with a variety of autoimmune disorders and investigated whether aPS/PT could be used as diagnostic test in patients suspected of having APS. The study population comprised 219 patients with autoimmune diseases including 82 patients with APS and 137 without APS (55 systemic lupus erythematosus, 32 rheumatoid arthritis, 10 primary Sjogren's syndrome, 8 scleroderma, 5 Behcet's disease and 27 other rheumatic diseases). IgG/M aPS/PT were measured by ELISA using phosphatidylserine-prothrombin complex as antigen immobilized on ELISA plates in the presence of CaCl2. IgG/M aCL were measured by standard methods and LA was detected by clotting assays. aPS/PT, aCL and LA were more frequently found in patients with APS (47, 46 and 69, respectively) than in those without APS (11, 19 and 29, respectively) (OR 95% [CI]; 15.4 [7.2-32.7], 7.9 [4.1-15.2, 19.8 [9.6-40.6], respectively]. The sensitivity of each assay for the diagnosis of APS was 57%, 56% and 86% with a specificity of 92%, 86% and 79%, respectively. aPS/PT and aCL have similar diagnostic value for APS, therefore, we propose that aPS/PT should be further explored, not only for research purposes, but also as a candidate of one of the laboratory criteria for the classification of the APS. (c) 2004 Published by Elsevier Ltd.

Antiphospholipid antibody associated thrombocytopenia and the paradoxical risk of thrombosis
T Atsumi, S Furukawa, O Amengual, T Koike
LUPUS, 14, 7, 499, 504, ARNOLD, HODDER HEADLINE PLC, 2005年, ［査読有り］
英語, The pathogenesis of thrombocytopenia in patients with antiphospholipid syndrome (APS) is heterogeneous. Patients with antiphospholipid antibodies (aPL) and thrombocytopenia in the absence of clinical manifestations of APS will be diagnosed and treated as idiopathic thrombocytopenic purpura. However, the presence of aPL places those individuals at particular risk for developing both bleeding and thrombotic complications. Therefore, we propose the inclusion of such patients in the subgroup 'aPL-associated thrombocytopenia'. More attention should be devoted to this subgroup of patients to elucidate the role of aPL in the development of thrombocytopenia and to facilitate the adequate monitoring of its potential thrombotic risk.

Association of HLA-DM polymorphism with the production of antiphospholipid antibodies
ML Sanchez, K Katsumata, T Atsumi, FI Romero, ML Bertolaccini, A Funke, O Amengual, E Kondeatis, RW Vaughan, A Cox, GRV Hughes, MA Khamashta
ANNALS OF THE RHEUMATIC DISEASES, 63, 12, 1645, 1648, B M J PUBLISHING GROUP, 2004年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To investigate whether variation in the HLA-DM gene is important in producing a group of pathogenic autoantibodies-antiphospholipid antibodies (aPL)-on the basis that HLA class II restricted antigen presentation is involved in the production of aPL.
Methods: HLA-DMA and DMB polymorphisms were genotyped by polymerase chain reaction combined with restriction enzyme digestion in 51 white patients with primary antiphospholipid syndrome (APS), 82 with systemic lupus erythematosus (SLE) ( 42 with APS and 40 without APS), and 109 healthy white controls. The association with the aPL profile was examined.
Results: The distribution of DMA alleles in APS patients and in patients with APS associated with SLE was significantly different from that in controls by 4x2 chi(2) test with 3 degrees of freedom (p = 0.035 and 0.011, respectively), but it was not different between SLE patients without APS and controls. The allelic distribution of DMA was also different between patients with IgG class anticardiolipin antibody or those with lupus anticoagulant (LA) and controls (p = 0.012 and 0.007, respectively) and between patients with and without LA among SLE patients ( p = 0.035). All these differences included the increase in DMA*0102 in the former groups.
Conclusions: The results suggest that HLA-DMA*0102 or its linked gene(s) form one of the genetic risks for the production of aPL.

The p38 mitogen-activated protein kinase (MAPK) pathway mediates induction of the tissue factor gene in monocytes stimulated with human monoclonal anti-beta(2)Glycoprotein I antibodies
M Bohgaki, T Atsumi, Y Yamashita, S Yasuda, Y Sakai, A Furusaki, T Bohgaki, O Amengual, Y Amasaki, T Koike
INTERNATIONAL IMMUNOLOGY, 16, 11, 1633, 1641, OXFORD UNIV PRESS, 2004年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The anti-phospholipid syndrome (APS) is characterized by thrombosis and the presence of anti-phospholipid antibodies (aPL). Tissue factor (TF), the major initiator of the coagulation system, is induced on monocytes by aPL in vitro, explaining, in part, the pathophysiology in this syndrome. However, little is known regarding the nature of the aPL-induced signal transduction pathways leading to TF expression. In this study, we investigated aPL-inducible genes in PBMC using cDNA array system and real-time PCR. Our results indicated that the mitogen-activated protein kinase (MAPK) pathway was related to TF expression when PBMCs were treated, in the presence of beta(2)Glycoprotein I (beta(2)GPI), with human monoclonal anti-beta(2)GPI antibodies [beta(2)GPI-dependent anti-cardiolipin antibodies (aCL/beta(2)GPI)]. Western blotting studies using monocyte cell line (RAW264.7) demonstrated that p38 MAPK protein was phosphorylated with nuclear factor kappaB (NF-kappaB) activation by monoclonal aCL/beta(2)GPI treatment, and that SB203580, a specific p38 MAPK inhibitor, decreased the aCL/beta(2)GPI-induced TF mRNA expression. The p38 MAPK phosphorylation, NF-kappaB translocation and TF mRNA expression triggered by aCL/beta(2)GPI were abolished in the absence of beta(2)GPI. These results demonstrated that the p38 MAPK signaling pathway plays an important role in aPL-induced TF expression on monocytes and suggest that the p38 MAPK may be a possible therapeutic target to modify a pro-thrombotic state in patients with APS.

Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome
O Amengual, T Atsumi, T Koike
CLINICAL IMMUNOLOGY, 112, 2, 144, 149, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2004年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The preliminary classification criteria for definite anti phospholipid syndrome (APS) include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) as laboratory criteria. However, antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies comprising also antibodies against phospholipid-binding proteins or their complexes with phospholipids. Prothrombin is one of the antigen recognized by aPL. In the last decade, there has been increasing interest in antibodies against prothrombin alone and those against phosphatidylserine-prothrombin complex. The latter, phosphatidylserine-dependent antiprothrombin antibodies (aPT), have been closely associated with APS and LA. In this paper, we review the properties of anti prothrombin antibodies. (C) 2004 Elsevier Inc. All rights reserved.

Diagnostic value of antiagalactosyl IgG antibodies in rheumatoid arthritis
H Das, T Atsumi, Y Fukushima, H Shibuya, K Ito, Y Yamada, Y Amasaki, K Ichikawa, O Amengual, T Koike
CLINICAL RHEUMATOLOGY, 23, 3, 218, 222, SPRINGER-VERLAG, 2004年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Our objective in this study was to explore the diagnostic value of antiagalactosyl IgG antibodies in rheumatoid arthritis (RA). The study comprised 266 Japanese patients with systemic autoimmune diseases, including 60 with RA. Human agalactosyl IgG was prepared enzymatically, and the serum levels of antiagalactosyl IgG antibodies were determined using a lectin enzyme immunoassay. Serum IgG and IgM rheumatoid factors (RF) were measured using laser nephelometry for IgM (LN-RF) and an enzyme-linked immunosorbent assay for IgG (IgG-RF). Antiagalactosyl IgG antibodies were significantly more common in patients with RA than in those without (78% vs. 18%, odds ratio (OR) 16.51, 95% confidence interval (CI) 8.12-33.58, p<0.0001). Patients with RA also had a higher frequency of LN-RF than those without RA (75% vs. 28%, OR 7.81, 95% CI 3.91-15.58, p< 0.001). The specificity of antiagalactosyl IgG antibodies for RA was significantly higher than that of LN-RF (82% vs. 72%, p<0.0011). There was a significant correlation between titers of antiagalactosyl IgG antibodies and C-reactive protein levels. Antiagalactosyl IgG antibodies are more specific markers for RA than conventional LN-RF, and may provide useful information for the diagnosis of RA.

Nicked beta(2)-glycoprotein I: a marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis
S Yasuda, T Atsumi, M Ieko, E Matsuura, K Kobayashi, J Inagaki, H Kato, H Tanaka, M Yamakado, M Akino, H Saitou, Y Amasaki, S Jodo, O Amengual, T Koike
BLOOD, 103, 10, 3766, 3772, AMER SOC HEMATOLOGY, 2004年05月, ［査読有り］
英語, 研究論文（学術雑誌）, beta(2)-Glycoprotein I (beta(2)-GPI) is proteolytically cleaved by plasmin in domain V (nicked beta(2)-GPI), being unable to bind to phospholipids. This cleavage may occur in vivo and elevated plasma levels of nicked P2-GPI were detected in patients with massive plasmin generation and fibrinolysis turnover. In this study, we report higher prevalence of elevated ratio of nicked P2-GPI against total beta(2)-GPI in patients with ischemic stroke (63%) and healthy subjects with lacunar infarct (27%) when compared to healthy subjects with normal findings on magnetic resonance imaging (8%), suggesting that nicked beta(2)-GPI might have a physiologic role beyond that of its parent molecule in patients with thrombosis. Several inhibitors of extrinsic fibrinolysis are known, but a negative feedback regulator has not been yet documented. We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K-D Of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta2-GPI and the fifth kringle domain of Glu-plasminogen. Nicked beta(2-)GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta2-GPI lacks these properties. These data suggest that beta(2)-GPI/plasmin-nicked beta(2)-GPI controls extrinsic fibrinolysis via a negative feedback pathway loop. (C) 2004 by The American Society of Hematology.

Tissue factor in antiphospholipid syndrome: shifting the focus from coagulation to endothelium
O Amengual, T Atsumi, MA Khamashta
RHEUMATOLOGY, 42, 9, 1029, 1031, OXFORD UNIV PRESS, 2003年09月, ［査読有り］
英語

Cerebral imaging by magnetic resonance imaging and single photon emission computed tomography in systemic lupus erythematosus with central nervous system involvement
K Oku, T Atsumi, S Furukawa, T Horita, Y Sakai, S Jodo, Y Amasaki, K Ichikawa, O Amengual, T Koike
RHEUMATOLOGY, 42, 6, 773, 777, OXFORD UNIV PRESS, 2003年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. To assess the significance of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) abnormalities in patients with systemic lupus erythematosus (SLE).
Methods. Forty-four patients with SLE were retrospectively analysed. Patients were classified into three groups [1 and 2: patients with central nervous system (CNS) manifestations before and after starting high-dose steroid therapy, respectively; 3: patients without CNS manifestations. MRI was performed in all 44 patients and SPECT in 31.
Results. Abnormal findings in MRI were found in 19 patients. MRI abnormalities were significantly more frequent in patients with CNS manifestations than in those without [71 vs 17%, odds ratio (OR) 11.9, confidence interval (CI) 2.8-49.9, P=0.0003]. After the initiation of steroid therapy, patients with CNS manifestations also had an increased frequency of abnormal MRI. No correlation was found between SPECT findings and CNS manifestations. However, patients with CNS manifestations after starting steroids showed a markedly increased frequency of abnormal MRI and SPECT compared with those without CNS manifestations (80 vs 7%; OR 56, CI 4.4-719, P=0.0003). The positive predictive value of abnormality in both techniques in developing CNS manifestations after starting steroids was 89%.
Conclusion. MRI findings correlated with CNS manifestations in SLE. Where there is a high suspicion of CNS involvement, the combination of MRI and SPECT may be useful in predicting CNS manifestations after starting steroid therapy.

Specificities, properties, and clinical significance of antiprothrombin antibodies
O Amengual, T Atsumi, T Koike
ARTHRITIS AND RHEUMATISM, 48, 4, 886, 895, WILEY-LISS, 2003年04月, ［査読有り］
英語

Actualización en el Sindrome Antifosfolipido　　　　　　　　　　　　　　　
Amengual Olga
Inmunologia, 21, 159, 163, 2002年, ［査読有り］, ［招待有り］
スペイン語

HLA class II gene polymorphisms in antiphospholipid syndrome: haplotype analysis in 83 Caucasoid patients
R Caliz, T Atsumi, E Kondeatis, O Amengual, MA Khamashta, RW Vaughan, JS Lanchbury, GRV Hughes
RHEUMATOLOGY, 40, 1, 31, 36, OXFORD UNIV PRESS, 2001年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives. We investigated the association between HLA class II haplotypes and antiphospholipid syndrome (APS).
Methods. HLA DRB1, DQB1 and DQA1 genotypes were determined by the polymerase chain reaction using sequence-specific primers in 83 Caucasoid British patients with APS. The genotype frequencies were compared between subgroups of patients acid 177 healthy controls.
Results. DPB1*0604/5/6/7/9-DQA1*0102-DRB1*1302 and DQB1*0303-DQA1*0201-DRB1*0701 haplotypes showed significantly positive correlations with APS [P = 0.0087 and P = 0.0012, respectively]. The association of the former was enhanced in primary APS patients with anti-beta2-glycoprotein I antibodies (anti-beta 2GPI) [odds ratio 6.2, 95% confidence interval (2.2-17.6). P = 0.0014, corrected P = 0.042].
Conclusions. These alleles and haplotypes might affect anti-beta 2GPI production and APS development in different and heterogeneous fashion.

An evaluation of an angiotensin-converting enzyme gene polymorphism and the risk of arterial thrombosis in patients with the antiphospholipid syndrome
NM Lewis, K Katsumata, T Atsumi, ML Sanchez, FI Romero, ML Bertolaccini, A Funke, O Amengual, MA Khamashta, GRV Hughes
ARTHRITIS AND RHEUMATISM, 43, 7, 1655, 1656, LIPPINCOTT WILLIAMS & WILKINS, 2000年07月, ［査読有り］
英語, 研究論文（学術雑誌）

Antiphospholipid antibodies in leprotic patients: A correlation with disease manifestations
A Elbeialy, K Strassburger-Lorna, T Atsumi, ML Bertolaccini, O Amengual, M Hanafi, MA Khamashta, GRV Hughes
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 18, 4, 492, +, CLINICAL & EXPER RHEUMATOLOGY, 2000年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives
Previous studies showed that antiphospholipid antibodies (aPL) are frequent in the sera of leprosy patients and are most probably directed against body tissue cardiolipins. Some groups have demonstrated differences between the binding specificity of "autoimmune-aPL" and "non-autoimmune-aPL". It is widely accepted that a plasma protein beta 2-Glycoprotein I (beta 2-GPI), is required for the binding of autoimmune anticardiolipin antibodies (aCL) to cardiolipin. However, some reports suggested heterogeneity of leprosy aCL with respect to their beta 2-Glycoprotein I (beta 2GPI) dependency, although no thromboembolic complications have been reported. This study was designed to assess the specificity of aPL by investigating the prevalence of aCL, anti-phosphatidylserine (aPS), anti-phosphatidylinositol (aPI), anti-beta 2GPI and antiprothrombin (aPT) antibodies, and evaluate their clinical significance in a group of patients with lepromatous leprosy.
Patients and methods
35 lepromatous leprosy patients were selected randomly from an Egyptian leprosarium as a study group. 35 normal household contact controls were selected matching the study group for both sex and age. aCL, aPS, aPI, aPT, anti-beta 2GPI and beta 2-dependent aCL antibodies were investigated by ELISA in all patients and controls.
Results
aCL antibodies were more frequent in leprosy patients than in controls [13/35 (37%) vs. 3/35 (9%), respectively, p = 0.02] and significantly correlated with Raynaud's phenomenon, skin modules, chronic skin ulcers and urticarial skin rash. No association was found with hypopigmentation, hyperpigmentation and saddle nose. None of the patients presented aPS nor aPI. Only 1 subject from the control group presented aPI along with aCL. aPT were present in 2/35 (5.7%) and anti-beta 2GPI in 1/35 (2.9%) leprotic patients. None of the individuals from the control group presented aPT nor anti-beta 2GPI.
Conclusions
An association was found between the presence of aCL and certain dermatological manifestations of leprosy, such as Raynaud's phenomenon, skin nodules, chronic skin ulcers and urticarial skin rash. As in other infectious diseases, there was a lack of beta 2GPI-dependency and an absence of thrombotic complications.

Association of antiphosphatidylserine/prothrombin autoantibodies with HLA class II genes
ML Bertolaccini, T Atsumi, AR Caliz, O Amengual, MA Khamashta, GRV Hughes, T Koike
ARTHRITIS AND RHEUMATISM, 43, 3, 683, 688, LIPPINCOTT WILLIAMS & WILKINS, 2000年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. To investigate the associations between HLA class II genes and antiphosphatidylserine/prothrombin antibodies (aPS/PT) in a group of British caucasoid patients with antiphospholipid antibodies (aPL),
Methods. This study included 82 patients with aPL, IgG aPS/PT were detected in sera using enzyme-linked immunosorbent assays. HLA-DQB1, DQA1, and DRB1 genotypes were determined by polymerase chain reaction using sequence-specific primers. All results were compared with 177 matched healthy control subjects.
Results. IgG aPS/PT were present in 41 of 82 patients (50%), The frequencies of DQB1*0301/4, DQB1*0604/5/6/7/9, and DRB1*1302 alleles were increased in patients with aPS/PT compared with controls. To minimize the interference of the association between anti-beta(2)-glycoprotein I (anti-beta(2)GPI) and HLA, patients with anti-beta(2)GPI were excluded from further analyses, and only HLA-DQB1*0301/4 remained significant compared with controls (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.2-6.5, P < 0.03), In the haplotype analysis, HLA-DQB1*0301/4;DQA1*0301/2;DRB1*04 was significantly increased in patients with IgG aPS/PT compared with controls (OR 4.75, 95% CI 1.72-13.10, P = 0.0063),
Conclusion, The HLA-DQB1*0301/4;DQA1*0301/2;DRB1*04 haplotype and its components may influence the production of aPS/PT in the antiphospholipid syndrome, which partly explains the correlation between the lupus anticoagulant and DQB1*03.

Comment on the article Apolipoprotein (a) deposition in atherosclerotic coronary arteries of a patient with systemic lupus erythematosus by Asanuma et al.　　　　　　　　　　　　　　　
Atsumi T, Amengual O, Khamashta MA, Romero FI, Hughes GRV
Arthritis Rheum ., 43, 2142, 2000年, ［査読有り］
英語

Oxidized lipoproteins and the antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual, O, Atsumi T, Khamashta MA
Seminars Clinical Immunol, 1, 21, 27, 2000年, ［査読有り］
英語

Autoantibodies against malondialdehyde-modified lipoprotein(a) in antiphospholipid syndrome
FI Romero, T Atsumi, FJ Tinahones, JM Gomez-Zumaquero, O Amengual, MA Khamashta, GRV Hughes
ARTHRITIS AND RHEUMATISM, 42, 12, 2606, 2611, LIPPINCOTT WILLIAMS & WILKINS, 1999年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. To demonstrate the existence of antibodies that react against malondialdehyde (MDA)modified lipoprotein(a) (MDA-Lp[a]), a molecule that exhibits behavioral similarities to MDA-modified low-density lipoprotein (MDA-LDL), and to assess the possible relationship of these antibodies (anti-MDA-Lp[a]) to anti-MDA-LDL antibodies (anti-MDA-LDL) in the antiphospholipid syndrome (APS),
Methods. We studied 104 patients with APS (61 with primary APS and 43 with APS secondary to systemic lupus erythematosus) and 106 healthy controls. Anti-MDA-Lp(a) were measured by enzyme-linked immunosorbent assay (ELISA) using MDA-Lp(a) as antigen, Plasma levels of Lp(a) were determined, Anti-MDA-LDL, anticardiolipin antibodies (aCL), and anti-beta(2)-glycoprotein I antibodies (anti-beta(2)GPI) were also measured by ELISA, Inhibition assays were performed to determine the presence of crossreactivity between anti-MDA-Lp(a) and anti-MDA-LDL,
Results. Anti-MDA-Lp(a) were detected in 38 of 104 patients (37%) but in only 6 of 106 controls (6%) (chi(2) = 28, P < 0.0001), Levels of anti-MDA-Lp(a) were also higher in patients than in controls (P < 0.0001). Titers of these antibodies did not correlate with plasma levels of Lp(a), The presence of anti-MDA-Lp(a) was significantly associated with that of anti-MDA-LDL (chi(2) = 22.09, P < 0.0001). There was a strong correlation between the titers of anti-MDA-Lp(a) and anti-MDA-LDL (r = 0.59, P < 0.0001), and inhibition assays showed significant cross-reactivity between the 2 populations of antibodies, Anticardiolipin antibodies and anti-beta(2)GPI were present in sera from 67 patients (64%) and 48 patients (46%), respectively, No correlation was found between the titer of anti-MDA-Lp(a) and titers of either aCL or anti-beta(2)GPI,
Conclusion, We report for the first time the existence of autoantibodies against MDA-Lp(a), The presence of antibodies reacting not only against MDA-LDL but also against MDA-Lp(a) supports the hypothesis of a role for oxidative phenomena in the pathogenesis of APS and atherosclerosis.

Correlation between beta 2-glycoprotein I valine/leucine(247) polymorphism and anti-beta 2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome
T Atsumi, A Tsutsumi, O Amengual, MA Khamashta, GRV Hughes, Y Miyoshi, K Ichikawa, T Koike
RHEUMATOLOGY, 38, 8, 721, 723, OXFORD UNIV PRESS, 1999年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives. beta 2-Glycoprotein I (beta 2GPI) exon 7 polymorphism leads to a valine-leucine amino acid exchange at position 247 in domain 5 of beta 2GPI, between the phospholipid binding site and the cryptic site of the epitopes for anti-beta 2CPI antibodies. Therefore, position 247 polymorphism may affect the conformational change of beta 2GPI and the exposure of the epitopes for anticardiolipin antibodies (aCL) (= anti-beta 2GPI antibodies). In this study we analysed the genetic polymorphism of beta 2GPI in a British cohort of well-defined antiphospholipid syndrome (APS) patients.
Methods. This study comprised 88 Caucasoid patients with APS [57 with primary APS and 31 with APS secondary to systemic lupus erythematosus (SLE)]. Polymorphism assignment was determined by polymerase chain reaction followed by allele-specific restriction enzyme digestion (PCR-RFLP). The presence of anti-beta 2GPI antibodies was detected by ELISA utilizing irradiated ELISA plates.
Results and conclusions. Anti-beta 2CPI antibodies were present in 28 of 57 primary APS patients (49%) and in 19 of 31 secondary APS patients (61%). The allele containing valine(247) was significantly more frequent in primary APS patients with anti-beta 2GPT antibodies than in controls (OR = 2.51, 95% CI 1.03-6.13, P = 0.0396) or in primary APS patients without anti-beta 2GPI antibodies (OR = 2.92, 95% CI 1.16-7.39, Y = 0.0204). This tendency was not found in the secondary APS group. In conclusion, the beta 2GPT polymorphism, valine/leucine(247), is correlated with anti-beta 2GPI antibody production in patients with primary APS, and valine247 may be important in the formation of beta 2GPI antigenicity.

Risk of thrombosis in patients with antiphospholipid antibodies and factor V Leiden mutation
JL Pablos, RA Caliz, PE Carreira, T Atsumi, L Serrano, O Amengual, B Santiago, MA Khamashta, GRV Hughes, JJ Gomez-Reino
JOURNAL OF RHEUMATOLOGY, 26, 3, 588, 590, J RHEUMATOL PUBL CO, 1999年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Antiphospholipid antibodies (aPL) are thrombophilic risk markers in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). The risk factors for recurrent venous or arterial thrombosis and indications for longterm anticoagulation therapy are debated. We hypothesized that carrying a second thrombophilic defect, factor V Leiden mutation, would increase the risk for thrombosis in patients with aPL.
Methods. Seventy-five patients with primary APS and 83 with SLE and aPL with or without thrombosis followed at 2 university hospitals were studied. Factor V mutation rate was analyzed in patients and in 200 healthy blood donors by polymerase chain reaction analysis.
Results. The prevalence of factor V Leiden mutation in patients with SLE and aPL or primary APS was similar to controls. Patients with deep vein thrombosis or arterial thrombosis did not have a significantly increased rate of factor V mutation compared to controls or to patients with aPL without thrombosis.
Conclusion, Factor V Leiden mutation is not significantly associated with vein thrombosis in patients with aPL. However, due to the sample size we cannot rule out synergy between both factor V Leiden and aPL. A trend toward increased risk for thrombosis was detected in patients with the mutation and this should be analyzed in a larger study.

Antibodies to beta(2)-glycoprotein I: A potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus
SS Sanfilippo, MA Khamashta, T Atsumi, O Amengual, ML Bertolaccini, D D'Cruz, N Amft, GT Swana, GRV Hughes
JOURNAL OF RHEUMATOLOGY, 25, 11, 2131, 2134, J RHEUMATOL PUBL CO, 1998年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective, To clarify risk factors for the development of clinical features of antiphospholipid syndrome (APS) in patients with anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE).
Methods, We studied 65 SLE patients, all with positive IgG and/or IgM aCL. Patients were divided into 2 groups; I: 29 SLE patients with features of APS (SLE/APS) and II: 36 aCL positive SLE patients without any feature of APS (SLE/aCL). Serum samples were collected from our serum bank. Anti-beta(2)-glycoprotein I (anti-beta(2)-GPI) were tested by ELISA using irradiated plates in the absence of cardiolipin. Anti-dsDNA antibodies were tested by standard Farr assay.
Results. There were no major differences between SLE clinical manifestations in both groups. However, the frequency of IgG anti-beta(2)-GPI was markedly increased in SLE/APS (18/29, 62%) than in SLE/aCL (4/36, 11%) (chi-squared 18.6, p = 0.0001). The levels of anti-dsDNA antibodies in the same samples were slightly lower in SLE/APS.
Conclusion. Our data suggest that increased levels of IgG anti-beta(2)-GPI may be a specific feature of SLE/APS patients rather than reflecting a polyclonal B cell activation.

Multiple antiphospholipid tests do not increase the diagnostic yield in antiphospholipid syndrome
ML Bertolaccini, B Roch, O Amengual, T Atsumi, MA Khamashta, GRV Hughes
BRITISH JOURNAL OF RHEUMATOLOGY, 37, 11, 1229, 1232, OXFORD UNIV PRESS, 1998年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The family of antiphospholipid antibodies (aPL) includes a heterogeneous population of autoantibodies whose specificity is directed against not only phospholipids, but their complex with plasma proteins. Anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) tests are widely performed to screen the aPL family which is associated with thrombotic complications in patients with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). The clinical significance of other aPL tests, including antibodies against phosphatidylserine (aPS), phosphatidylinositol (aPI), phosphatidic acid (aPA), phosphatidyl choline (aPC) and phosphatidylethanolamine (aPE), has not been established. The purpose of this study was to evaluate whether multiple aPL tests have enhanced diagnostic value for APS. We tested IgG/M/A aPS, aPI, aPA, aPC and aPE by ELISA using 10% bovine serum as blocking and sample diluent in 26 SLE patients with clinical manifestations of APS, but negative for both aCL and LA (Group 1). The results were compared with 32 SLE patients without any features of APS (Group 2) and 24 SLE patients with APS (aCL and/or LA positive) (Group 3). In Group 1, 1/26 (4%) was positive for IgA aPE, less frequent than in other groups, and none of the patients had any other aPL. In Group 2, 1/32 (3%) was positive for aPS, two (6%) for aPI, one (3%) for aPA and four (12.5%) for aPE. None was positive for aPC. In the third group, 13/24 (54%) were positive for aPS, 11 (46%) for aPI, 15 (63%) for aPA, four (17%) for aPC and seven (29%) for aPE. Since aPE was found in some patients, we extended the study, including 207 SLE patients, and tested aPE. IgG/M/A aPE was found in six (3%), 10 (5%) and 21 (10%), respectively, but no association was found between aPE and any clinical features of APS. This study suggests that screening by multiple aPL tests does not increase the diagnostic yield in APS.

Arterial disease in lupus and secondary antiphospholipid syndrome: Association with anti-beta2-glycoprotein I antibodies but not with antibodies against oxidized low-density lipoprotein
FI Romero, O Amengual, T Atsumi, MA Khamashta, FJ Tinahones, GRV Hughes
BRITISH JOURNAL OF RHEUMATOLOGY, 37, 8, 883, 888, OXFORD UNIV PRESS, 1998年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The prevalence and clinical significance of antibodies against beta(2)-glycoprotein I (anti-beta(2)GPI) and antibodies against oxidized low-density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta(2)GPI and IgG anti-ox-LDL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta(2)GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta(2)GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta(2)GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta(2)GPI was found. These results suggest that IgG anti-beta(2)GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.

IgG2 restriction of anti-beta(2)-glycoprotein I as the basis for the association between IgG2 anticardiolipin antibodies and thrombosis in the antiphospholipid syndrome: Comment
O Amengual, T Atsumi, MA Khamashta, ML Bertolaccini, GRV Hughes
ARTHRITIS AND RHEUMATISM, 41, 8, 1513, 1514, LIPPINCOTT WILLIAMS & WILKINS, 1998年08月, ［査読有り］
英語

Prothrombin mutation is not associated with thrombosis in patients with antiphospholipid syndrome
ML Bertolaccini, T Atsumi, BJ Hunt, O Amengual, MA Khamashta, GRV Hughes
THROMBOSIS AND HAEMOSTASIS, 80, 1, 202, 203, F K SCHATTAUER VERLAG GMBH, 1998年07月, ［査読有り］
英語

Autoantibodies to human prothrombin and clinical manifestations in 207 patients with systemic lupus erythematosus
ML Bertolaccini, T Atsumi, MA Khamashta, O Amengual, GRV Hughes
JOURNAL OF RHEUMATOLOGY, 25, 6, 1104, 1108, J RHEUMATOL PUBL CO, 1998年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. Prothrombin (factor II) is one of the phospholipid binding proteins with a procoagulant property. Some publications have shown the presence of autoantibodies against prothrombin (aPT) in patients with antiphospholipid antibodies (aPL). We assessed the clinical significance of aPT in thrombotic events in patients with systemic lupus erythematosus (SLE).
Methods. IgG and IgM aPT were tested by ELISA in 207 patients with SLE,
Results. Fifty-eight patients (28%) had positive aPT (> mean + 3 SD of 100 controls). Twenty-eight (14%) had IgG alone, 21 (10%) IgM alone, and 9 (4%) had both IgG and IgM, Patients with aPT had a history of thrombosis more frequently than those without aPT [31/58 (53%) vs 47/149 (32%), chi-squared = 7.6, p = 0.006]. No correlation was found between the presence of aPT and clinical features of SLE.
Conclusion. aPT are frequently found in patients with SLE, and are a potential marker for thrombosis.

Binding of anticardiolipin antibodies to protein C via beta(2)-glycoprotein I (beta(2)-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system
T Atsumi, MA Khamashta, O Amengual, S Donohoe, Mackie, I, K Ichikawa, T Koike, GRV Hughes
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 112, 2, 325, 333, WILEY-BLACKWELL, 1998年05月, ［査読有り］
英語, 研究論文（学術雑誌）, It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via beta(2)-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of beta(2)-GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of beta(2)-GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL(+) patients had a positive titre in the presence of cardiolipin (CL) and beta(2)-GPI, but binding was not found in the absence of beta(2)-GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of beta(2)-GPI and that of anti-beta(2)-GPI antibody (r=0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, beta(2)-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of beta(2)-GPI to protein C and its phospholipid dependency were investigated. beta(2)-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of beta(2)-GPI (virtually anti-beta(2)-GPI antibodies) was evaluated in the presence of cardiolipin and beta(2)-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and beta(2)-GPI, whereas they did not in the absence of either beta(2)-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and beta(2)-GPI, leading to protein C dysfunction.

Arterial disease and thrombosis in the antiphospholipid syndrome - A pathogenic role for endothelin 1
T Atsumi, MA Khamashta, RS Haworth, G Brooks, O Amengual, K Ichikawa, T Koike, GRV Hughes
ARTHRITIS AND RHEUMATISM, 41, 5, 800, 807, LIPPINCOTT WILLIAMS & WILKINS, 1998年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. To explore a possible correlation between endothelin 1 (ET-1), the most potent endothelium-derived contracting factor that modulates vascular smooth muscle tone, and arterial disease in patients with the antiphospholipid syndrome (APS),
Methods. Plasma levels of ET-1 were measured in APS patients with (n = 16) and without (n = 11) arterial thrombosis and in non-APS patients with arterial thrombosis (n = 9), In addition, steady-state prepro-ET-l messenger RNA (mRNA) levels were determined in endothelial cells treated with a range of human monoclonal anticardiolipin antibodies (aCL) (as anti-beta(2)-glycoprotein I antibodies) by semiquantitative P-32-dCTP-labeled reverse transcription-polymerase chain reaction.
Results. Compared with healthy controls, markedly increased plasma levels of ET-1 were found in APS patients with arterial thrombosis (2.00 +/- 0.87 versus 0.96 +/- 0.37 pg/ml; P = 0.0001) but not in other groups. Three human monoclonal aCL induced prepro-ET-l mRNA levels significantly more than did control monoclonal antibody lacking aCL activity,
Conclusion. Plasma ET-1 levels correlated significantly with a history of arterial thrombosis in patients with APS. Prepro-ET-l mRNA was induced by human monoclonal aCL in the in vitro experimental system. The induction of ET-1 by antiphospholipid antibodies might contribute to increased arterial tone, leading to vasospasm and, ultimately, to arterial occlusion.

Fc gamma receptor IIA H/R131 polymorphism in patients with antiphospholipid antibodies
T Atsumi, R Caliz, O Amengual, MA Khamashta, GRV Hughes
THROMBOSIS AND HAEMOSTASIS, 79, 5, 924, 927, F K SCHATTAUER VERLAG GMBH, 1998年05月, ［査読有り］
英語, 研究論文（学術雑誌）, A role for Fc gamma receptor in the pathophysiology of thrombosis in APS has been hypothesized. The polymorphism of this receptor, Fc gamma RIIA H/R131, is associated with the binding affinity for human IgG(2) (i.e. Fc gamma RIIA-H131 isoform has a higher affinity than Fc gamma RIIA-R131). Since anti-beta(2) glycoprotein I antibodies (anti beta(2)GPI), which play a major pathogenic role in APS, show IgG(2) dominant distribution, we investigated the prevalence of receptor isoforms in patients with antiphospholipid antibodies (aPL) by a PCR-RFLP method. We studied 100 Caucasian patients with aPL. (57 primary APS, 32 secondary APS to SLE and II other diseases with aPL) and 41 healthy controls. H131/H131, H131/R131 and R131/R131 genotypes were found in 21 (21%), 50 (50%) and 19 (29%) in the patient group, and 9 (22%). 23 (56%) and 9 (22%) in control group, respectively. Thus there was no statistically significant difference in the prevalence of each genotype in these groups. None of the clinical manifestations of primary APS (arterial/venous thrombosis, recurrent pregnancy loss and thrombocytopenia) was significantly correlated with any Fc gamma RIIA genotype. In conclusion, Fc gamma RIIA polymorphism did not correlate with the manifestations of APS, and Fc gamma IIA genotype is not a genetic marker of APS.

The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome
O Amengual, T Atsumi, MA Khamashta, GRV Hughes
THROMBOSIS AND HAEMOSTASIS, 79, 2, 276, 281, F K SCHATTAUER VERLAG GMBH, 1998年02月, ［査読有り］
英語, 研究論文（学術雑誌）, The antiphospholipid syndrome (APS) is characterised by both arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopaenia in association with antiphospholipid antibodies (aPL). To explore further the pathogenesis of thrombosis in APS, we evaluated the behaviour of tissue factor (TF) pathway in patients with APS. Plasma antigen levels of soluble TF and tissue factor pathway inhibitor (TFPI), a physiological regulator of TF dependent coagulation activation, were measured in 57 APS patients (36 primary and 21 secondary to systemic lupus erythematosus). Significantly elevated levels of both TF and TFPI were found in AP-S patients compared with 25 healthy controls (279 +/- 15 vs. 217 +/- 17 pg/ml, p = 0.01; 56.24 +/- 2.00 vs. 47.92 +/- 2.22 ng/ml, p = 0.01, respectively), suggesting in vivo upregulation of TF pathway in patients with APS. By flow-cytometry, monocytes from a healthy donor displayed higher TF antigen expression when incubated in the presence of APS plasmas than in control plasmas (24.23 +/- 3.11 vs. 12.78 +/- 1.57%, p = 0.002). Peripheral blood mononuclear cells (PBMC) also expressed more procoagulant activity (PCA) when incubated in the presence of APS plasmas than in control plasmas (1.80 +/- 0.12 vs. 1.35 +/- 0.054, p = 0.001) implying that TF up-regulation in APS was reproducible in vitro. Human monoclonal anticardiolipin antibodies induced PCA on PBMC and also TF mRNA on both PBMC and human umbilical vein endothelial cells shown by reverse-transcription polymerase chain reaction. These data strongly suggest that the TF pathway is implicated in the pathogenesis of aPL related thrombosis.

Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome
T Atsumi, MA Khamashta, C Andujar, MJ Leandro, O Amengual, PRJ Ames, GRV Hughes
JOURNAL OF RHEUMATOLOGY, 25, 1, 69, 73, J RHEUMATOL PUBL CO, 1998年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective. To assess the significance of lipoprotein(a) [Lp(a)], a risk factor for atherothrombosis, and its relationship with fibrinolysis in a cohort of patients with antiphospholipid syndrome (APS).
Methods. Plasma levels of Lp(a) were measured in 68 patients with APS (42 primary, 26 secondary to systemic lupus erythematosus),
Results. Elevated plasma levels of Lp(a) were found in patients with APS compared to 22 healthy controls (p = 0.0001). The significance persisted after comparing Lp(a) levels in 3 APS subgroups (arterial thrombosis, n = 37; venous thrombosis, n = 31; recurrent miscarriages, n = 24) with those of controls (p < 0.0001). Patients with APS with maximal elevation of Lp(a) showed a lower fibrinolytic activity (lower D-dimer and higher plasminogen activator inhibitor) than patients whose Lp(a) was within a normal range.
Conclusion. These findings suggest that Lp(a) may represent a marker of APS and that Lp(a) has a negative effect on the fibrinolytic system that might contribute to the thrombotic tendency of APS.

Most anticardiolipin antibodies in mixed connective tissue disease are beta(2)-glycoprotein independent - Reply
Mendonça LLF, Amengual O, Atsumi T, Khamashta MA, Hughes GRV
JOURNAL OF RHEUMATOLOGY, 25, 1, 189, 190, J RHEUMATOL PUBL CO, 1998年01月, ［査読有り］
英語

Advances in antiphospholipid (Hughes') syndrome.
Amengual O, Atsumi T, Khamashta MA, Hughes GR
Annals of the Academy of Medicine, Singapore, 27, 61, 66, 1, 1998年01月, ［査読有り］

Anti-beta(2)-glycoprotein I antibody testing in patients with antiphospholipid syndrome - Reply
MA Khamashta, O Amengual, T Atsumi
BRITISH JOURNAL OF RHEUMATOLOGY, 36, 11, 1235, 1235, OXFORD UNIV PRESS, 1997年11月, ［査読有り］
英語

Autoantibodies against oxidized low-density lipoprotein in antiphospholipid syndrome
O Amengual, T Atsumi, MA Khamashta, F Tinahones, GRV Hughes
BRITISH JOURNAL OF RHEUMATOLOGY, 36, 9, 964, 968, OXFORD UNIV PRESS, 1997年09月, ［査読有り］
英語, 研究論文（学術雑誌）, The prevalence and clinical significance of anti-oxidized low-density lipoprotein antibodies (anti-ox-LDL) were evaluated in patients with the antiphospholipid syndrome (APS). Anti-ox-LDL were measured in the sera of 107 patients with APS (64 primary APS, 43 secondary to systemic lupus erythematosus) by enzyme-linked immunosorbent assay (ELISA) utilizing malondialdehyde (MDA)-modified LDL as antigen. In the same patients, anticardiolipin antibodies (aCL) and anti-beta 2-glycoprotein I antibodies (anti-beta 2GPI) were also measured. A positive titre of anti-ox-LDL was detected in 22% of patients, but only in 6% of control subjects (chi(2) = 12, P = 0.0005). Levels of anti-ox-LDL were higher in patients with arterial thrombosis (n = 58) than in those without (n = 49) (P = 0.0001). Anti-ox-LDL levels correlated weakly with those of aCL (r = 0.196, P = 0.043), but not with those of anti-beta 2GPI (r = 0.076). Our findings suggest that elevated levels of anti-sx-LDL may represent another potential marker of APS, particularly of patients prone to arterial thrombosis.

Lipids and atherosclerosis in systemic lupus erythematosus　　　　　　　　　　　　　　　
Ames PRJ, Amengual O, Atsumi T, Khamashta MA
Lipidos Research, 1, 17, 19, 1997年, ［査読有り］, ［招待有り］
英語

Significado clínico de los anticuerpos antifosfolípido　　　　　　　　　　　　　　　
Amengual O, Cuadrado MJ, Khamashta MA
Jano, 3, 58, 60, 1997年, ［査読有り］, ［招待有り］
スペイン語

Up-regulated tissue factor expression in antiphospholipid syndrome
T Atsumi, MA Khamashta, O Amengual, GRV Hughes
THROMBOSIS AND HAEMOSTASIS, 77, 1, 222, 223, F K SCHATTAUER VERLAG GMBH, 1997年01月, ［査読有り］
英語

Specificity of ELISA for antibody beta 2-glycoprotein I in patients with antiphospholipid syndrome
O Amengual, T Atsumi, MA Khamashta, T Koike, GRV Hughes
BRITISH JOURNAL OF RHEUMATOLOGY, 35, 12, 1239, 1243, OXFORD UNIV PRESS, 1996年12月, ［査読有り］
英語, 研究論文（学術雑誌）, The clinical significance of anti-beta 2 glycoprotein I (beta 2-GPI) antibodies was evaluated in patients with antiphospholipid syndrome (APS), primary and secondary to systemic lupus erythematosus (SLE): Anti-beta 2-GPI were tested in 120 patients (39 primary APS, 32 APS with SLE and 49 SLE without APS) by ELISA utilizing irradiated plates in the absence of cardiolipin. Anticardiolipin antibodies (aCL) and antiphosphatidylserine antibodies were also measured in the same patients using standardized assays. Anti-beta 2-GPI titres correlated strongly to those of aCL (r = 0.816, P = 0.0001), and to those of antiphosphatidylserine antibodies (r = 0.841, P = 0.0001). Anti-beta 2-GPI were detected in 53.5% of APS patients (38/71), but only in 4.1% of SLE patients without APS (2/49). In the latter group, 24.5% (12/49) of patients had a positive titre of aCL. The anti-beta 2-GPI assay showed higher specificity for APS than the aCL in APS (96 as 75%, respectively, chi(2) = 6.75, P = 0.00094). Our findings suggest that the assay of anti-beta 2-GPI may improve the specificity for APS.

Clinical significance of anti-beta(2)-glycoprotein I antibodies
O Amengual, T Atsumi, MA Khamashta, GRV Hughes
ANNALES DE MEDECINE INTERNE, 147, 15, 17, MASSON EDITEUR, 1996年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Antiphospholipid antibodies are a heterogeneous group of autoantibodies with clinical importance because of their strong association with thrombotic events. Recent evidence have shown that antiphospholipid antibodies are not directed against phospholipids, as has previously been thought, but are a part of a large family of autoantibodies against phospholipid-binding plasma proteins. So far, one of the most common and best characterized antigenic target is beta(2)-glycoprotein I (beta(2)-GPI), which plays an important role in the binding of anticardiolipin antibodies (aCLA) to cardiolipin. The detection of anti-beta(2)-GPI antibodies by using a simple and rapid ELISA may facilitate the recognition of <<pathogenic>> aCL in antiphospholipid syndrome.

Anticuerpos antifosfolípido　　　　　　　　　　　　　　　
Cuadrado MJ, Amengual O, Khamashta MA
Rev Esp Reumatol, 23, 389, 395, 1996年, ［査読有り］, ［招待有り］
スペイン語

Reasons for breastfeeding avoidance: a multicenter insight in mothers with systemic lupus erythematosus.　　　　　　　　　　　　　　　
Foddai SG, Radin M, Schreiber K, Cecchi I, Signorelli F, De Jesús G, Aso K, Kono M, Urban ML, Bacco B, Gallo Cassarino S, Lo Sardo L, Arbrile M, Barinotti A, Gómez García I, Quaglia MI, Tissera Y, Gervasoni F, Aguirre-Zamorano MA, Alba P, Benedetto C, Atsumi T, Amengual O, et al, Annals of Rheumatic diseases, 82, supp 1, 1483, 2023年05月
英語

Relationship between fish consumption and response to treatment with molecular targeted therapies in patients with rheumatoid arthritis　　　　　　　　　　　　　　　
Tarumi M, Amengual O, Navidad Fuentes M, Yasuda M, Kosumi Y, Takeyama S, Yoshimura M, Ninagawa K, Aso K, Hisada R, Kono M, Fujieda Y, Kato M, Cáliz Cáliz R, Atsumi T, Annals of Rheumatic diseases, 82, supp 1, 1421, 2023年05月, ［筆頭著者］
英語

Effect of consumption of fish rich in n-3 polyunsaturated fatty acids on treatment response in patients with rheumatoid arthritis.　　　　　　　　　　　　　　　
Amengual O, Tarumi M, Fujieda Y, Hisada R, Kono M, Kato M, Atsumi T, 22nd International Union of Nutritional Sciences International Congress of Nutrition (IUNS-ICN), Tokyo, Japan 6-1, PAB(T4), 206, 2022年12月, ［筆頭著者］

Study of the effect of fish consumption on treatment response in rheumatoid arthritis.　　　　　　　　　　　　　　　
Amengual Olga, Third meeting of the Association of Spanish Researchers in Japan., 2022年11月, ［筆頭著者］
スペイン語

関節リウマチ患者の魚の摂取量と分子標的治療の治療経過との関連　　　　　　　　　　　　　　　
垂水 政人, Amengual O, 安田 充孝, 小住 由衣, 竹山脩平, 吉村 大, 久田 諒, 河野 通仁, 藤枝 雄一郎, 加藤 将, 渥美 達也, 第37回日本臨床リウマチ学会 札幌, 2022年10月
日本語

Antiphospholipd Syndrome International Research Collaboration　　　　　　　　　　　　　　　
Amengual O, The 16th symposium of the academic standardization committee of the Japanese society of thrombosis and hemostasis Saturday, 第16回日本血栓止血学会学術標準化委員会シンポジウム, 2022年02月, ［招待有り］

抗リン脂質抗体症候群患者における新型コロナワクチン投与後の抗リン脂質抗体価の変動に関する検討
藤枝雄一郎, 安田充孝, 奥健志, AMENGUAL Olga, 渥美達也, 日本血栓止血学会学術標準化委員会シンポジウム, 16th, 2022年02月

Functional MRIによる動的機能連関解析を用いた炎症性関節炎患者における治療効果予測
崎山広大, 阿部靖矢, 藤枝雄一郎, 多田麻里亜, 守谷悠, 安田充孝, 久田諒, 河野通仁, 加藤将, AMENGUAL Olga, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 37th, 2022年

関節リウマチ患者のニューモシスチス肺炎に対するサラゾスルファピリジンの一次予防効果
吉村大, 河野通仁, 阿部靖矢, 久田諒, 藤枝雄一郎, 加藤将, アメングアル オルガ, 大庭幸治, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 37th, 2022年

iPSCを介した全身性硬化症関連肺動脈高血圧特異的内皮細胞の確立とその機能および分子解析【JST・京大機械翻訳】|||
KUDO Yuki, KATO Masaru, SHIBATA Yuhei, KONO Michihito, FUJIEDA Yuichiro, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

全身性硬化症関連間質性肺疾患の程度の定量的バイオマーカーとしてのKrebs von den Lunge-6【JST・京大機械翻訳】|||
TADA Maria, KATO Masaru, SAKIYAMA Kodai, TSUCHIDA Naohisa, NISHINO Kokoro, MORIYA Haruka, YASUDA Mitsutaka, NINAGAWA Keita, KONO Michihito, FUJIEDA Yuichiro, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

JAK1は関節リウマチ滑膜線維芽細胞においてオートファジーを制御し,炎症および自己免疫能を増強する【JST・京大機械翻訳】|||
NINAGAWA Keita, KATO Masaru, YOSHIMURA Masaru, KUDO Yuki, KONO Michihito, FUJIEDA Yuichiro, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

多発性血管炎を伴う好酸球性肉芽腫症患者における不可逆的運動神経障害の予測因子【JST・京大機械翻訳】|||
TSUCHIDA Naohisa, KONO Michihito, SAKIYAMA Kodai, TADA Maria, NISHINO Kokoro, MORIYA Haruka, YASUDA Mitsutaka, ASO Kuniyuki, NINAGAWA Keita, YOSHIMURA Masaru, TAKEYAMA Shuhei, KOSUMI Yui, TARUMI Masato, FUJIEDA Yuichiro, KATO Masaru, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

全身性エリテマトーデス患者における脳血管炎の臨床的特徴:症例シリーズ研究【JST・京大機械翻訳】|||
TARUMI Masato, FUJIEDA Yuichiro, KOSUMI Yui, TAKEYAMA Shuhei, ASO Kuniyuki, ABE Nobuya, KONO Michihito, KATO Masaru, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

関節リウマチおよび脊椎関節炎における生物学的製剤に対する反応と関連した動的機能的連結性【JST・京大機械翻訳】|||
SAKIYAMA Kodai, ABE Nobuya, FUJIEDA Yuichiro, TADA Maria, TSUCHIDA Naohisa, NISHINO Kokoro, MORIYA Haruka, YASUDA Mitsutaka, KONO Michihito, KATO Masaru, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

関節リウマチ患者におけるニューモシスチス肺炎の予防としてのサラゾスルファピリジン:後ろ向き傾向スコアマッチングコホート研究【JST・京大機械翻訳】|||
YOSHIMURA Masaru, ABE Nobuya, KONO Michihito, FUJIEDA Yuichiro, KATO Masaru, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

維持療法中の低血小板レベルは全身性エリテマトーデス(DORIS)における寛解の定義を達成するための失敗と関連する【JST・京大機械翻訳】|||
TAKEYAMA Shuhei, KONO Michihito, ASO Kuniyuki, FUJIEDA Yuichiro, KATO Masaru, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

Epstein-Barrウイルス再活性化の改善とともに寛解に至った難治性関節リウマチの一例
徳井秀大, 崎山広大, 加藤将, 多田麻里亜, 土田直央, 西野慶, 守谷悠, 安田充孝, 河野通仁, 藤枝雄一郎, AMENGUAL Olga, 渥美達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 66th, 2022年

Intake of fish rich in n-3 polyunsaturated fatty acids is associated with good response to treatment in rheumatoid arthritis patients receiving targeted therapies.　　　　　　　　　　　　　　　
Tarumi M, Amengual O, Fujieda Y, Navidad Fuentes M, Tsuchida N, Yasuda M, Nishino K, Kosumi Y, Takeyama S, Yoshimura M, Ninagawa K, Aso K, Kono M, Kato M, Cáliz Cáliz R, Atsumi T, Annals of Rheumatic diseases, 81, 1, 1229, 2022年

Disease activity at conception predicts lupus flare up to 2 years after birth: a multicentre long term follow-up study.　　　　　　　　　　　　　　　
M. Radin, K. Schreiber, I. Cecchi, F. Signorelli, G. De Jesùs, K. Aso, M. Kono, M. L. Urban, B. Bacco, S. Gallo Cassarino, L. Lo Sardo, S. G. Foddai, A. Barinotti, I. Gómez García, M. I. Quaglia, Y. Tissera, F. Gervasoni, M. Á. Aguirre-Zamorano, P. Alba, C. Benedetto, T. Atsumi, O. Amengual, et al, Annals of the Rheumatic disease, 81, 1, 1356, 2022年

藤枝雄一郎、安田充孝、奥健志、Olga Amengual、渥美達也　　　　　　　　　　　　　　　
藤枝雄一郎、安田充孝、奥健志、Olga Amengual、渥美達也, APSレジストリの進捗」、第9回学術集会日本抗リン脂質抗体標準化ワークショップ、東京, 2021年12月

「抗リン脂質抗体症候群患者における新型コロナウイルスワクチン投与後の抗リン脂質抗体プロファイルの変化」　　　　　　　　　　　　　　　
藤枝雄一郎, 安田充孝, 奥健志, Olga Amengual, 渥美達也, 第9回学術集会日本抗リン脂質抗体標準化ワークショップ 東京, 2021年12月

抗リン脂質抗体症候群における IgM型抗リン脂質抗体と血栓発症リスクに関する検討　　　　　　　　　　　　　　　
藤枝雄一郎, Olga Amengual, 佐藤太貴, 河野通仁, 加藤将, 奥健志, 渥美達也, 第43回日本血栓止血学会学術集会, Web, 2021年05月

関節リウマチにおけるニューモシスチス肺炎に対するサラゾスルファピリジンの予防効果:後向き傾向スコアマッチングコホート研究
YOSHIMURA Masaru, ABE Nobuya, KONO Michihito, FUJIEDA Yuichiro, KATO Masaru, OKU Kenji, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 65th, 2021年

全身性硬化症関連間質性肺疾患の患者のiPS細胞と分化内皮細胞の確立
KUDO Yuki, KATO Masaru, SHIBATA Yuhei, KONO Michihito, FUJIEDA Yuichiro, AMENGUAL Olga, OKU Kenji, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 65th, 2021年

Lupus-Proneマウスにおけるミクログリアの特異的発現遺伝子の同定
KARINO Kohei, KONO Michihito, KUDO Yuki, KANDA Masatoshi, KANDA Masatoshi, ABE Nobuya, FUJIEDA Yuichiro, KATO Masaru, OKU Kenji, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 65th, 2021年

全身性エリテマトーデスにおけるループス腸炎の新規バイオマーカーとしての抗gAChR抗体
ASO Kuniyuki, KONO Michihito, ABE Nobuya, FUJIEDA Yuichiro, KATO Masaru, OKU Kenji, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 65th, 2021年

PR3-ANCA陽性であった巨細胞性動脈炎の一例
多田麻里亜, 藤枝雄一郎, 崎山広大, 土田直央, 西野慶, 守谷悠, 安田充孝, 河野通仁, 加藤将, 奥健志, OLGA Amengual, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 49th, 2021年

ギラン・バレー症候群様の神経症状を呈した好酸球性多発血管炎性肉芽腫症の二例
西野慶, 藤枝雄一郎, 崎山広大, 多田麻里亜, 土田直央, 守谷悠, 安田充孝, 河野通仁, 加藤将, OLGA Amengual, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 36th, 2021年

ナルコレプシーを呈した神経精神ループスの1例
田畑智章, 守谷悠, 藤枝雄一郎, 崎山広大, 多田麻里亜, 土田直央, 西野慶, 安田充孝, 河野通仁, 加藤将, OLGA Amengual, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 36th, 2021年

セクキヌマブの中止で自然消退した乾癬,シェーグレン症候群合併節外性辺縁帯リンパ腫の一例
崎山広大, 河野通仁, 近祐次郎, 多田麻里亜, 土田直央, 西野慶, 守谷悠, 安田充孝, 藤枝雄一郎, 加藤将, OLGA Amengual, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 36th, 2021年

Prediction of responder and non-responder to JAK inhibitors in patients with rheumatoid arthritis: A pilot study with integrative cluster analysis　　　　　　　　　　　　　　　
Sugawara M, Fujieda Y, Noguchi A, Tanimura S, Shimizu Y, Nagakawa I, Takahashi H, Kono M, Kato M, Oku K, Amengual O, Atsumi T, Prediction of responder and non-responder to JAK inhibitors in patients with rheumatoid arthritis: A pilot study with integrative cluster analysis, 2020年11月

The Association Between the Risk of Venous Thromboembolism andDisease Activity in Patients with Rheumatoid Arthritis:A Retrospective Observational Study　　　　　　　　　　　　　　　
Yoshimura M, Fujieda Y, Kono Michihito, Kato M, Oku K, Amengual O, Atsumi T, The American College of Rheumatology Convergence 2020 Annual Meeting, virtual congress, 2020年11月

原発性抗リン脂質症候群患者における全身性エリテマトーデス発症の危険因子
OGATA Yusuke, FUJIEDA Yuichiro, SATO Taiki, OHNISHI Naoki, KONO Michihito, KATO Masaru, OKU Kenji, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年08月

The risk assessment of developing deep venous thrombosis in patients with rheumatoid arthritis
YOSHIMURA Masaru, FUJIEDA Yuichiro, KONO Michihito, KATO Masaru, OKU Kenji, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年08月

The prothrombin/MHC class II complexes on procoagulant cells as the novel immune target for pathogenic antiphospholipid antibodies.　　　　　　　　　　　　　　　
Fujieda Y, Ohnishi N, Kono M, Kato M, Oku K, Amengual O, Arase H, Atsumi T, The International Society on Thrombosis and Haemostasis 2020 Virtual Congress, 2020年07月

抗リン脂質抗体症候群患者におけるクラスター分析を用いた長期予後の解析
尾形裕介, 藤枝雄一郎, 菅原正成, 佐藤太貴, 大西直樹, 河野通仁, 加藤将, 奥健志, AMENGUAL Olga, 渥美達也, 日本血栓止血学会誌, 31, 2, 2020年

ループス腸炎の臨床的特徴と再燃の危険因子に関する検討
麻生邦之, 河野通仁, 藤枝雄一郎, 加藤将, 奥健志, AMENGUAL Olga, 保田晋助, 渥美達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年

IgM抗リン脂質抗体の長期持続と血栓症リスク
SATO Taiki, AMENGUAL Olga, FUJIEDA Yuichiro, OHNISHI Naoki, ABE Nobuya, KONO Michihito, KATO Masaru, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年

皮膚筋炎患者における血管炎由来症状に対する危険因子
KARINO Kohei, KONO Michihito, KONO Michihiro, KURITA Takashi, ABE Nobuya, FUJIEDA Yuichiro, KATO Masaru, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年

全身性硬化症関連肺動脈高血圧症特異的内皮細胞の確立とトランスクリプトーム解析
KUDO Yuki, KATO Masaru, SHIBATA Yuhei, KONO Michihito, FUJIEDA Yuichiro, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年

全身性硬化症関連肺動脈高血圧症患者における左心疾患表現型の評価
NINAGAWA Keita, KATO Masaru, KONO Michihito, FUJIEDA Yuichiro, OKU Kenji, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年

マウスにおいて抗リン脂質抗体が認知機能およびミクログリア活性化に及ぼす影響
ABE Nobuya, OKU Kenji, KUDO Yuki, KARINO Kohei, KONO Michihito, FUJIEDA Yuichiro, AMENGUAL Olga, KATO Masaru, KAMIMURA Daisuke, YASUDA Shinsuke, MURAKAMI Masaaki, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 64th (CD-ROM), 2020年

IgM antiphospholipid antibodies: long term follow-up and thrombotic risk.　　　　　　　　　　　　　　　
Sato T, Amengual O, Fujieda Y, Nakamura H, Ohnishi N, Abe N, Kono M, Kato M, Oku K, Toshiyuki Bohgaki, T, Yasuda S, Atsumi T, Congress for the International Society on Thrombosis and Haemostasis Melbourne Australia, 2019年06月

疾患特異的iPS細胞を用いた強皮症性肺動脈性肺高血圧症の病態解明
工藤友喜, 加藤将, 柴田悠平, 神田真聡, リー ウェンシー, 河野通大, 菅原恵理, 河野通仁, 藤枝雄一郎, 坊垣暁之, アメングアル オルガ, 奥健志, 保田晋助, 渥美達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

オートファジーは滑膜線維芽細胞においてビメンチンのシトルリン化と主要組織適合性複合体クラスIIとの相互作用を促進する
SUGAWARA Eri, KATO Masaru, KUDO Yuki, LEE Wenshi, KONO Michihito, FUJIEDA Yuichiro, BOHGAKI Toshiyuki, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

プロコアグラント細胞に発現するプロトロンビン/MHCクラスII複合体は,病原性抗リン脂質抗体の標的である
OHNISHI Naoki, FUJIEDA Yuichiro, KONO Michihito, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

全身性エリテマトーデス患者における神経精神医学的フレアの予測因子
ASO Kuniyuki, KONO Michihito, KONO Michihiro, NINAGAWA Keita, SATO Taiki, WATANABE Toshiyuki, SHIMIZU Yuka, FUJIEDA Yuichiro, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, OLGA Amengual, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

炎症性関節炎の生物製剤への不十分な反応に関連する疼痛処理領域の強化された静止状態機能的結合
ABE Nobuya, FUJIEDA Yuichiro, KARINO Kohei, KONO Michihito, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

筋膜炎症は皮膚筋炎における急速進行性間質性肺疾患の新規リスク因子である:全身MRIを用いた研究
KARINO Kohei, KONO Michihiro, KONO Michihito, ABE Nobuya, FUJIEDA Yuichiro, KATO Masaru, BOHGAKI Toshiyuki, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

結合組織病患者の妊娠合併症のリスク分析:母体および胎児の転帰に関する単一施設後向き研究
SUGAWARA Eri, KATO Masaru, KUDO Yuki, LEE Wenshi, KONO Michihito, FUJIEDA Yuichiro, BOHGAKI Toshiyuki, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

全身性エリテマトーデス患者における精神神経ループスを伴うflareの危険因子に関する検討
麻生邦之, 河野通仁, 河野通大, 蜷川慶太, 佐藤太貴, 渡邉俊之, 清水裕香, 藤枝雄一郎, 加藤将, 奥健志, AMENGUAL Olga, 保田晋助, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

抗リン脂質抗体症候群の長期予後
佐藤太貴, 藤枝雄一郎, 大西直樹, 麻生邦之, 蜷川慶太, 河野通仁, 加藤将, 奥健志, OLGA Amengual, 保田晋助, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

当科における膠原病合併妊娠コホート
菅原恵理, 菅原恵理, 加藤将, 河野通仁, 藤枝雄一郎, AMENGUAL Olga, 奥健志, 保田晋助, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

患者由来iPS細胞を用いた強皮症性肺動脈性肺高血圧症の病態解明
工藤友喜, 加藤将, 柴田悠平, リー ウェンシー, 河野通大, 菅原恵理, 河野通仁, 藤枝雄一郎, 坊垣暁之, AMENGUAL Olga, 奥健志, 保田晋助, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

MRIで米粒体を認めた全身性エリテマトーデス患者の非結核性抗酸菌性腱鞘滑膜炎の1例
蜷川慶太, 藤枝雄一郎, 松井雄一郎, 神島保, 麻生邦之, 佐藤太貴, 河野通仁, 加藤将, 奥健志, OLGA Amengual, 保田晋助, 岩崎倫政, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

単球細胞表面上のプロトロンビン/MHCクラスII分子複合体はホスファチジルセリン依存性抗プロトロンビン抗体の新規対応抗原である
大西直樹, 藤枝雄一郎, 河野通仁, 加藤将, 奥健志, AMENGUAL Olga, 保田晋助, 荒瀬尚, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

関節リウマチ患者の滑膜線維芽細胞においてRANKL発現をオプチニューリンは負制御する
LEE Wen Shi, 加藤將, 菅原恵理, 河野通大, 工藤友喜, 河野通仁, 藤枝雄一郎, 坊垣暁之, AMENGUAL Olga, 奥建志, 保田晋助, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

オートファジー受容体オプチニューリンは関節リウマチの患者由来の滑膜線維芽細胞におけるRANKL発現を負に制御する
LEE Wen Shi, KATO Masaru, SUGAWARA Eri, KONO Michihiro, HISADA Ryo, KUDO Yuki, KONO Michihito, FUJIEDA Yuichiro, BOHGAKI Toshiyuki, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

滑膜線維芽細胞におけるオートファジー受容体オプチニューリンは関節リウマチにおける関節破壊に対して保護的役割を果たす
LEE Wen Shi, KATO Masaru, SUGAWARA Eri, KONO Michihiro, KUDO Yuki, KONO Michihito, FUJIEDA Yuichiro, BOHGAKI Toshiyuki, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本免疫学会総会・学術集会記録(CD-ROM), 48, 2019年

抗リン脂質抗体症候群患者に対する第Xa因子阻害薬とワルファリンの比較検討
佐藤太貴, 中村浩之, 藤枝雄一郎, 大西直樹, 麻生邦之, 蜷川慶太, 阿部靖矢, 河野通仁, 加藤将, 奥健志, 坊垣暁之, アメングアル オルガ, 保田晋助, 渥美達也, 日本血栓止血学会誌, 30, 2, 2019年

マウスモデルにおける抗リン脂質抗体の精神神経症状や中枢神経系細胞への影響
阿部靖矢, 阿部靖矢, 奥健志, 狩野皓平, 河野通仁, 藤枝雄一郎, AMENGUAL Olga, 田中勇希, 上村大輔, 保田晋助, 村上正晃, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 47th, 2019年

Efficacy of treatments for antiphospholipid antibody associated thrombocytopenia: A systematic review and meta-analysis.　　　　　　　　　　　　　　　
Abe N, Oku K, Amengual O, Fujieda Y, Kato M, Bohgaki T, Yasuda S, Mori R, Morishita E, Suzuki-Inoue K, Atsumi T, The 10th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis, Sapporo, Japan, 2018年06月

Antiphospholipid score is a novel risk factor for idiopathic osteonecrosis of the femoral head.　　　　　　　　　　　　　　　
Kato M, Hisada R, Fujieda Y, Oku K, Bohgaki T, Amengual O, Yasuda S, Atsumi, The 10th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis, Sapporo, Japan, 2018年06月

抗リン脂質抗体症候群における抗血小板薬二剤併用療法の血栓予防効果と安全性の検討
大西直樹, 藤枝雄一郎, 久田諒, 中村浩之, 加藤将, 奥健志, 坊垣暁之, AMENGUAL Olga, 保田晋助, 渥美達也, 日本血栓止血学会誌, 29, 2, 2018年

抗リン脂質抗体症候群における末梢血リンパ球サブセットおよび抗体産生機序の解明
久田諒, 加藤将, 菅原恵理, 藤枝雄一郎, 奥健志, 坊垣暁之, AMENGUAL Olga, 保田晋助, 渥美達也, 日本血栓止血学会誌, 29, 2, 2018年

抗リン脂質抗体スコアを用いた特発性大腿骨頭壊死発生リスク評価
加藤将, 久田諒, 菅原恵理, 藤枝雄一郎, 奥健志, 坊垣暁之, AMENGUAL Olga, 保田晋助, 渥美達也, 日本血栓止血学会誌, 29, 2, 2018年

抗リン脂質抗体症候群の長期予後
藤枝雄一郎, 大西直樹, 久田諒, 中村浩之, 奥健志, 坊垣暁之, AMENGUAL Olga, 保田晋助, 渥美達也, 日本血栓止血学会誌, 29, 2, 2018年

抗リン脂質抗体関連血小板減少症に対する治療法:システマティックレビューとメタ解析
阿部靖矢, 奥健志, AMENGUAL Olga, 藤枝雄一郎, 加藤将, 坊垣暁之, 保田晋助, 森臨太郎, 森下英理子, 井上克枝, 渥美達也, 日本血栓止血学会誌, 29, 2, 2018年

10年間の抗リン脂質抗体症候群患者の罹患率と死亡率:日本人患者157例の縦断コホート研究
OHNISHI Naoki, FUJIEDA Yuichiro, KONO Michihiro, TANIMURA Syun, HISADA Ryo, SUGAWARA Eri, NAKAMURA Hiroyuki, SHIMAMURA Sanae, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

血小板減少症関連抗リン脂質抗体の管理における既存治療法の有効性と安全性:システマティックレビューとメタ分析
ABE Nobuya, OKU Kenji, OLGA Amengual, FUJIEDA Yuichiro, KATO Masaru, BOHGAKI Toshiyuki, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

形質芽細胞の増殖は,Toll様受容体7多型およびI型インターフェロンの上方制御と関連し,抗リン脂質抗体症候群における抗体産生に寄与する
HISADA Ryo, KATO Masaru, SUGAWARA Eri, FUJIEDA Yuichiro, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

形質芽球増殖はToll様受容体7多形性と関係し,抗リン脂質症候群の患者における自己抗体産生に寄与する
HISADA Ryo, KATO Masaru, SUGAWARA Eri, FUJIEDA Yuichiro, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本免疫学会総会・学術集会記録(CD-ROM), 47, 2018年

オートファジーは,滑膜線維芽細胞におけるビメンチンのシトルリン化を促進する
SUGAWARA Eri, KATO Masaru, HISADA Ryo, FUJIEDA Yuichiro, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

結合組織疾患に関連した肺高血圧症における心臓磁気共鳴と右心カテーテル法を併用した右室機能評価と予後予測
ABE Nobuya, KATO Masaru, KARINO Kohei, SHIMOYAMA Shuhei, NAKAMURA Hiroyuki, NOGUCHI Atsushi, FUJIEDA Yuichiro, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

オートファジーは滑膜線維芽細胞におけるビメンチンのシトルリン化および主要組織適合複合体クラスIIとの相互作用を促進する
SUGAWARA Eri, KATO Masaru, KONO Michihito, FUJIEDA Yuichiro, BOHGAKI Toshiyuki, AMENGUAL Olga, OKU Kenji, YASUDA Shinsuke, ATSUMI Tatsuya, 日本免疫学会総会・学術集会記録(CD-ROM), 47, 2018年

ANCA関連血管炎患者60例に対するシクロフォスファミド間欠静注療法またはリツキシマブによる寛解導入療法
狩野皓平, 藤枝雄一郎, 阿部靖矢, 下山修平, 谷村瞬, 加藤将, 奥健志, 坊垣暁之, アメングアル オルガ, 保田晋助, 渥美達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

Sjoegren症候群を背景としたTAFRO症候群の一例
宮本郁未, 阿部靖矢, 狩野皓平, 下山修平, 藤枝雄一郎, 加藤将, 奥健志, 坊垣暁之, アメングアル オルガ, 保田晋助, 渥美達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

肺病変を有する関節リウマチ患者の長期予後
下山修平, 藤枝雄一郎, 阿部靖矢, 狩野皓平, 加藤将, 奥健志, 坊垣暁之, アメングアル オルガ, 保田晋助, 渥美達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 62nd, 2018年

全身MRIを用いた脊椎関節炎の評価
麻生邦之, 加藤将, 阿部靖矢, 谷村瞬, 河野通仁, 藤枝雄一郎, 奥健志, 坊垣暁之, アメングアル オルガ, 保田晋助, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 33rd, 2018年

Possible therapeutics for antiphospholipid antibody related thrombocytopenia: a systemic review and meta-analysis
Abe N, Oku K, Amengual O, Fujieda Y, Kato M, Bohgaki T, Yasuda S, Mori R, Morishita E, Suzuki-Inoue K, Tatsuya, Atsumi T, ACR/ARHP Annual Meeting in San Diego, CA, 69, 2017年11月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

New subset for antiphospholipid antibodies for diagnosis of antiphospholipid syndrome　　　　　　　　　　　　　　　
Oku K, Kanetsuka Y, Amengual O, Yasuda S, Ieko M, Atsumi T, The Scientific and Standardization Committee, International Society of Thrombosis and Haemostasis, Berlin, Germany, 2017年07月

HIGH RISK OF IDIOPATHIC OSTEONECROSIS IN SLE PATIENTS WITH HIGH ANTIPHOSPHOLIPID SCORE AND HYPERTRIGLYCERIDEMIA
R. Hisada, M. Kato, N. Ohnishi, M. Kono, S. Tanimura, E. Sugawara, H. Nakamura, K. Ohmura, S. Shimamura, Y. Fujieda, K. Oku, T. Bohgaki, O. Amengual, S. Yasuda, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 76, 598, 598, 2017年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

USEFULNESS OF SERUM HAPTOGLOBIN LEVELS AS A NOVEL MARKER FOR PULMONARY ARTERIAL HYPERTENSION COMPLICATED WITH CONNECTIVE TISSUE DISEASE
H. Nakamura, M. Kato, M. Kono, S. Tanimura, R. Hisada, E. Sugawara, K. Ohmura, S. Shimamura, Y. Fujieda, K. Oku, T. Bohgaki, O. Amengual, S. Yasuda, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 76, 624, 625, 2017年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

AUTOANTIBODY AGAINST COMPLEMENT COMPONENT 1Q SUBCOMPONENT IS ASSOCIATED WITH THE PATHOGENESIS OF RECURRENT PREGNANCY LOSS
K. Ohmura, K. Oku, T. Kitaori, M. Kono, S. Tanimura, E. Sugawara, R. Hisada, H. Nakamura, S. Shimamura, Y. Fujieda, M. Kato, T. Bohgaki, O. Amengual, S. Yasuda, M. Sugiura-Ogasawara, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 76, 1453, 1454, 2017年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

抗リン脂質抗体症候群における末梢血リンパ球サブセットおよび一塩基多型(SNP)の解析　　　　　　　　　　　　　　　
久田 諒, 加藤 将, 菅原 恵理, 中村 浩之, 大村 一将, 中川 久子, 藤枝 雄一郎, 奥 健志, 坊垣 暁之, アメングアル・オルガ, 堀田 哲也, 保田 晋助, 渥美 達也, 日本血栓止血学会誌, 28, 2, 229, 229, 2017年04月
(一社)日本血栓止血学会, 日本語

抗リン脂質症候群の患者における再発動脈血栓症の予防
OHNISHI Naoki, FUJIEDA Yuichiro, OGATA Yusuke, ABE Sawako, KONO Michihiro, TANIMURA Shun, HISADA Ryo, SUGAWARA Eri, NAKAMURA Hiroyuki, OHMURA Kazumasa, SHIMAMURA Sanae, DOI Mototsugu, SHIMIZU Yuka, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

抗C1q抗体は補体活性化を介して再発流産の病因に寄与する
OHMURA Kazumasa, OKU Kenji, KITAORI Tamao, AMENGUAL Olga, KONO Michihiro, TANIMURA Shun, NAKAMURA Hiroyuki, SUGAWARA Eri, HISADA Ryo, SHIMAMURA Sanae, SHIMIZU Yuka, FUJIDEDA Yuichiro, KATO Masaru, BOHGAKI Toshiyuki, YASUDA Shinsuke, SUGIURA-OGASAWARA Mayumi, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

抗リン脂質抗体症候群における補体制御因子の解析
中村浩之, 奥健志, 藤枝雄一郎, 加藤将, 坊垣暁之, AMENGUAL Olga, 保田晋助, 渥美達也, 補体, 54, 1, 2017年

オートファジーは滑膜線維芽細胞におけるビメンチンのシトルリン化を促進する
SUGAWARA Eri, KATO Masaru, HISADA Ryo, FUJIEDA Yuichiro, OKU Kenji, BOHGAKI Toshiyuki, YASUDA Shinsuke, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

RasGRP4はRas-MARK経路を介して線維芽細胞様滑膜細胞の増殖を誘発する
SHIMAMURA Sanae, YASUDA Shinsuke, KONO Michihiro, NAKAMURA Hiroyuki, KONO Michihito, SHIMIZU Yuka, FUJIEDA Yuichiro, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

結合組織病の患者における血漿プレセプシン濃度の臨床的意義
TANIMURA Shun, FUJIEDA Yuichiro, KONO Michihiro, HISADA Ryo, SUGAWARA Eri, NAKAMURA Hiroyuki, OHMURA Kazumasa, SHIMAMURA Sanae, SHIMIZU Yuka, WATANABE Toshiyuki, SHIDA Haruki, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, HORITA Tetsuya, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

原発性抗リン脂質抗体症候群におけるH因子欠如に起因する補体第二経路の活性化
NAKAMURA Hiroyuki, OKU Kenji, ABE Sawako, OHNISHI Naoki, KONO Michihiro, TANIMURA Shun, HISADA Ryo, SUGAWARA Eri, OHMURA Kazumasa, SHIMAMURA Sanae, SHIMIZU Yuka, DOI Mototsugu, FUJIEDA Yuichiro, KATO Masaru, BOHGAKI Toshiyuki, AMENGUAL Olga, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

ループス腎炎患者の腎組織におけるインターフェロン誘導性Mx1蛋白質の発現
SHIMIZU Yuka, YASUDA Shinsuke, OHMURA Kazumasa, SHIMAMURA Sanae, SUGAWARA Eri, HISADA Ryo, KONO Michihiro, NAKAMURA Hiroyuki, FUJIEDA Yuchiro, KATO Masaru, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, HORITA Tetsuya, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 61st, 2017年

A patient-derived autoimmune IgG monoclonal anticardiolipin antibody that binds to beta 2 glycoprotein I domain I but not to total beta 2 glycoprotein I molecule.　　　　　　　　　　　　　　　
Oku K, Kanetsuka Y, Amengual O, Hisada R, Ohmura K, Kato M, Bohgaki T, Horita T, Yasuda S, Atsumi T, The 13th International Workshop on Autoantibodies and Autoimmunity, Kyoto, Japan,, 2016年10月

T細胞とB細胞サブセットの偏差及び抗リン脂質症候群の一塩基多型との関係
HISADA Ryo, KATO Masaru, KONO Michihiro, TANIMURA Shun, NAKAMURA Hiroyuki, SUGAWARA Eri, OHMURA Kazumasa, SHIMAMURA Sanae, SHIMIZU Yuka, NAKAGAWA Hisako, FUJIEDA Yuichiro, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, HORITA Tetsuya, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 68, 2016年10月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Preventive Effect of Combined Treatment with Bisphosphonate and Vitamin D on Atherosclerosis in Patients with Systemic Lupus Erythematosus
Kazumasa Ohmura, Masaru Kato, Toshiyuki Watanabe, Ryo Hisada, Masatoshi Kanda, Sanae Shimamura, Ikuma Nakagawa, Yuka Shimizu, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 68, 2016年10月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Anti-CCP Antibody Titers Decrease with Altered B-Cell Subpopulation in RA Patients Treated with Tocilizumab
Atsushi Noguchi, Shinsuke Yasuda, Ryo Hisada, Kazumasa Ohmura, Sanae Shimamura, Yuka Shimizu, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Miho Suzuki, Yoshihiro Matsumoto, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 68, 2016年10月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Complement Activation in Antiphospholipid Syndrome Due to the Multi-Activated Pathways of the Complement System
Hiroyuki Nakamura, Kenji Oku, Ryo Hisada, Kazumasa Ohmura, Masaru Kato, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 68, 2016年10月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

A Practical Application of Antiphospholipid Antibodies Profiles in the Diagnosis and Managements of Antiphospholipid Syndrome: The Modified Antiphospholipid Score
Kenji Oku, Olga Amengual, Kazumasa Ohmura, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Eriko Morishita, Masahiro Ieko, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 68, 2016年10月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Autoantibodies Against High Density Lipoprotein-Associated Proteins Are Related to Elevated Oxidized Low Density Lipoprotein Levels in Antiphospholipid Syndrome
Kenji Oku, Uhei Shibata, Joana Batuca, Olga Amengual, Michihiro Kono, Hiroyuki Nakamura, Ryo Hisada, Kazumasa Ohmura, Masaru Kato, Toshiyuki Bohgaki, Shinsuke Yasuda, Jose Delgado Alves, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 68, 2016年10月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

Effective procedure to diagnose antiphospholipid syndrome using the combination of anti-beta2-glycoprotein I domain I and phosphatidylserine-dependent antiprothrombin antibodies tests.　　　　　　　　　　　　　　　
Nakamura H, Oku K, Amengual O, Hisada R, Ohmura K, Kato M, Bohgaki T, Horita T, Yasuda S, Atsumi T, The 15th International Congress on Antiphospholipid Antibodies, Girne, Turkish Republic of Northern Cyprus, 2016年09月

INDUCTION OF TYPE-I INTERFERON MRNA IN HUMAN CD14+CELLS TREATED WITH NEUTROPHIL EXTRACELLULAR TRAPS
T. Bohgaki, S. Yasuda, M. Kato, K. Oku, O. Amengual, T. Horita, T. Atsumi, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 34, 4, S42, S42, 2016年07月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

抗リン脂質抗体測定の意義 スコア化について　　　　　　　　　　　　　　　
奥 健志, 家子 正裕, アメングアル・オルガ, 大村 一将, 加藤 将, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本検査血液学会雑誌, 17, 学術集会, S153, S153, 2016年07月
(一社)日本検査血液学会, 日本語

THROMBOCYTOPENIA IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES: A PARADOXICAL THROMBOTIC RISK FACTOR
R. Hisada, M. Kato, E. Sugawara, K. Ohmura, I. Nakagawa, K. Oku, T. Bohgaki, O. Amengual, T. Horita, S. Yasuda, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 75, 315, 315, 2016年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

抗リン脂質抗体陽性血小板減少症における血栓症発症リスク
久田 諒, 加藤 将, 大村 一将, 中川 育磨, 奥 健志, 坊垣 暁之, Amengual Olga, 堀田 哲也, 保田 晋助, 渥美 達也, 日本血栓止血学会誌, 27, 2, 222, 222, 2016年05月
(一社)日本血栓止血学会, 日本語

Screening for antiphospholipid syndrome diagnosis using non-criteria antiphospholipid antibody tests with a high positive predictive value: anti-beta2-glycoprotein I domain I and phosphatidylserine-dependent antiprothrombin antibodies　　　　　　　　　　　　　　　
Nakamura H, Oku K, Amengual O, Kato M, Bohgaki T, Horita T, Yasuda S, Atsumi T, 10th International Congress on Autoimmunity, Leipzig, Germany,, 2016年04月

抗β2糖蛋白質I領域Iとホスファチジルセリン依存性抗プロトロンビン抗体の併用は抗リン脂質抗体症候群の診断のための有効なスクリーニング法の候補となる可能性がある
NAKAMURA Hiroyuki, OKU Kenji, AMENGUAL Olga, KONO Michihiro, TANIMURA Shun, SHIBATA Yuhei, HISADA Ryo, SUGAWARA Eri, HATTORI Toshiyuki, OHMURA Kazumasa, SHIMAMURA Sanae, SHIDA Haruki, SHIMIZU Yuka, KATO Masaru, BOHGAKI Toshiyuki, HORITA Tetsuya, YASUDA Shinsuke, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 60th, 2016年04月

SLE・抗リン脂質抗体症候群 ループス腎炎 ループス腎炎の長期腎予後ならびに寛解導入治療に関する検討　　　　　　　　　　　　　　　
河野 通大, 保田 晋助, 河野 通仁, 谷村 瞬, 柴田 悠平, 久田 諒, 菅原 恵理, 中村 浩之, 服部 敏之, 大村 一将, 嶋村 抄苗, 志田 玄貴, 清水 裕香, 加藤 将, 奥 健志, 坊垣 暁之, オルガ・アメングアル, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 60回, 351, 351, 2016年03月
(一社)日本リウマチ学会, 日本語

SLE・抗リン脂質抗体症候群 精神神経ループス 全身性エリテマトーデス患者における動脈硬化進展の予測因子の検討　　　　　　　　　　　　　　　
大村 一将, 奥 健志, 渡邊 俊之, アメングアル・オルガ, 河野 通大, 谷村 瞬, 柴田 悠平, 中村 浩之, 久田 諒, 菅原 恵理, 服部 敏之, 嶋村 抄苗, 野口 淳史, 中川 育磨, 志田 玄貴, 清水 裕香, 加藤 将, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 60回, 352, 352, 2016年03月
(一社)日本リウマチ学会, 日本語

SLE・抗リン脂質抗体症候群 精神神経ループス 高用量ステロイド投与時に発症した全身性エリテマトーデスにおける精神神経症状の解析　　　　　　　　　　　　　　　
清水 裕香, 保田 晋助, 神田 真聡, 河野 通大, 久田 諒, 大村 一将, 嶋村 抄苗, 志田 玄貴, 加藤 将, 奥 健志, 坊垣 暁之, アメングアル・オルガ, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 60回, 353, 353, 2016年03月
(一社)日本リウマチ学会, 日本語

リウマチ性疾患の合併症 膠原病性肺高血圧症における予後不良因子の検討
中村 浩之, Amengual Olga, 河野 通大, 谷村 瞬, 柴田 悠平, 久田 諒, 菅原 恵理, 服部 敏之, 大村 一将, 嶋村 抄苗, 野口 淳史, 志田 玄貴, 清水 裕香, 加藤 将, 奥 健志, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 60回, 476, 476, 2016年03月
(一社)日本リウマチ学会, 日本語

抗燐脂質症候群の診断におけるIgGホスファチジルセリン依存性アンチプロトロンビン抗体試験
AMENGUAL Olga, OKU Takeshi, SUGIURA Mayumi, MURASHIMA Atsuko, ATSUMI Tatsuya, 日本臨床免疫学会会誌, 39, 4, 2016年

Rituximabにより寛解導入が得られた難治性ANCA関連血管炎症候群の5例
泉原里美, 大西直樹, 尾形裕介, 阿部早和子, 河野通大, 柴田悠平, 谷村瞬, 中村浩之, 土井基嗣, 加藤将, 奥健志, 坊垣暁之, AMENGUAL Olga, 堀田哲也, 保田晋助, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 31st, 2016年

Reduction of HLA Class II Expression and Beta-2-Glycoprotein I presentation by fluvastatin in Vitro and in Vivo: Possible mechanism of Statin-Induced-procoagulation in the Antiphospholipid Syndrome.　　　　　　　　　　　　　　　
Watanabe T, Oku K Amengual O, Hisada R Oomura K, Shida S, Shimizu Y, Kato M, Bohgaki T, Horita T, Yasuda S, Ishizu A, Arase H, Atsumi T, American College of Rheumatology, 79th Annual Scientific Meeting, San Francisco USA, 2015年11月

Procoagulant property of a novel patient-derived autoimmune IgG type monoclonal anticardiolipin antibody that binds to beta 2 glycoprotein domain I but not to total beta 2 glycoprotein I molecule.　　　　　　　　　　　　　　　
Oku K, Kanetsuka Y, Amengual O, Nakamura H, Oomura K, Bohgaki T, Horita T, Yasuda S, de Laat B, Atsumi T, American College of Rheumatology, 79th Annual Scientific Meeting, San Francisco USA, 2015年11月

Antiphospholipid antibodies as an quantitative marker: Comparison of antiphospholipid score and Global Anti-Phospholipid Syndrome Score (GAPSS).　　　　　　　　　　　　　　　
Oku K、Amengual, Nakamura H, Ohmura K, Kato M, Bohgaki T, Horita T, Yasuda S, Atsumi T, 30th Annual Meeting of Japan Society for Immunology of Reproduction, Kumamoto, Japan, 2015年11月

血栓症発症を予測する定量マーカーとしての抗リン脂質抗体 抗リン脂質抗体スコアとGlobal Anti-Phospholipid Syndrome Score(GAPSS)の比較　　　　　　　　　　　　　　　
奥 健志, オルガ・アメングアル, 中村 浩之, 久田 諒, 大村 一将, 加藤 将, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, Reproductive Immunology and Biology, 30, 1-2, 109, 109, 2015年11月
日本生殖免疫学会, 日本語

Questionnaire survey to sophomore medical students of Hokkaido University. What they expect of Medical English Practice.　　　　　　　　　　　　　　　
Murakami M, Amengual O, Kawabata W, Kohonaba M, Otaki J, The 47th Annual Meeting of the Japan Society for medical Education. Niigata, Japan, 2015年07月

Predictive markers for thrombotic events in autoimmune diseases: comparison of antiphospholipid score (APL-S) and global anti-phospholipid syndrome score (GAPSS)
K. Oku, O. Amengual, R. Hisada, K. Oomura, Nakagawa, I, T. Watanabe, T. Bohgaki, T. Horita, S. Yasuda, T. Atsumi, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 13, 775, 775, 2015年06月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

CARDIAC MAGNETIC RESONANCE IMAGING DETECTS DISEASE-SPECIFIC BIVENTRICULAR INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION
A. Noguchi, S. Yasuda, M. Kono, M. Kato, K. Oku, T. Bohgaki, O. Amengual, T. Horita, T. Sato, I. Tsujino, M. Nishimura, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 74, 1124, 1124, 2015年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

PROPHYLAXIS FOR THE PREVENTION OF OBSTETRIC COMPLICATIONS IN ASYMPTOMATIC WOMEN WITH ANTIPHOSPHOLIPID ANTIBODIES
O. Amengual, D. Fujita, E. Otta, L. Carmona, O. Kenji, M. Sugiura-Ogasawara, A. Murashima, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 74, 144, 144, 2015年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

SIGNIFICANCE OF IGG PHOSPHATIDYLSERINE-DEPENDENT ANTIPROTHROMBIN ANTIBODY TESTING FOR THE DIAGNOSIS OF ANTIPHOSPHOLIPID SYNDROME: RESULTS FROM THE INITIAL AND VALIDATION INTERNATIONAL MULTI-CENTRE STUDIES
O. Amengual, R. Forastiero, M. Sugiura-Ogasawara, K. Otomo, O. Kenji, C. Favas, J. Delgado Alves, P. Zigon, A. Ambrozic, M. Tomsic, I. Ruiz Arruza, G. Ruiz Irastorza, M. L. Bertolaccini, G. L. Norman, Z. Shums, A. Jiro, A. Murashima, A. E. Tebo, M. Gerosa, P. L. Meroni, I. Rodriguez-Pinto, R. Cervera, J. Swadzba, J. Musial, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 74, 155, 156, 2015年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

Myxovirus resistance protein 1 (Mx1) levels are elevated in T cells of the patients with SLE and serum Mx1 is a marker of Neuropsychiatric SLE
S. Yasuda, Y. Shimizu, M. Kono, S. Shimamura, A. Noguchi, H. Shida, T. Watanabe, M. Kato, K. Oku, T. Bohgaki, O. Amengual, T. Horita, T. Atsumi, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 33, 3, S20, S20, 2015年05月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

定量マーカーとしての抗リン脂質抗体 抗リン脂質抗体スコアとGAPSSの比較　　　　　　　　　　　　　　　
奥 健志, アメングアル・オルガ, 大村 一将, 中川 育磨, 渡邊 俊之, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本血栓止血学会誌, 26, 2, 185, 185, 2015年04月
(一社)日本血栓止血学会, 日本語

生物学的製剤を投与されている関節リウマチ患者の評価のための全身MRIの有用性
KONO Michihito, KONO Michihito, YASUDA Shinsuke, OHMURA Kazumasa, SHIMAMURA Sanae, NOGUCHI Atsushi, NAKAGAWA Ikuma, SHIDA Haruki, WATANABE Toshiyuki, SHIMIZU Yuka, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, HORITA Tetsuya, KAMISHIMA Tamotsu, ATSUMI Tatsuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 59th, 2015年

本邦における抗リン脂質抗体症候群関連妊娠合併症の診療の実際:内科医への質問表調査から
奥健志, 村島温子, 大村一将, Amengual Olga, 坊垣暁之, 堀田哲也, 保田晋助, 金子佳代子, 中西功, 野澤和久, 杉浦真弓, 渥美達也, 日本臨床免疫学会会誌, 38, 6, 2015年

P3-006 フルバスタチンはHLA classIIによるβ-2グリコプロテインIの抗原提示を抑制する
渡邊 俊之, 堀田 哲也, 保田 晋助, 石津 明洋, 荒瀬 尚, 渥美 達也, 奥 健志, アメングアル オルガ, 久田 諒, 大村 一将, 志田 玄貴, 清水 裕香, 加藤 将, 坊垣 暁之, 日本臨床免疫学会会誌, 38, 4, 326b, 326b, 2015年
【背景】HLA-DRB1*07:01は抗リン脂質抗体症候群（APS）の疾患感受性遺伝子である．近年，我々はβ2-グリコプロテインI（β2GPI）／HLA class II複合体が抗β2GPI抗体の対応抗原であることを報告した．スタチン製剤はいくつかのAPSモデルで抗β2GPI抗体による向血栓細胞活性化を抑制し，血栓症抑制効果が期待されていたが，その機序は不明である．【目的】抗β2GPI抗体による血栓傾向に対するスタチン製剤の抑制的作用機序を解明する．【方法】不死化ヒト臍帯静脈血管内皮細胞（HUEhT-1）とヒト単球系細胞（THP-1）にβ2GPIとHLA-DRA*01:01/DRB1*07:01（HLA-DR7）の遺伝子を導入した後，フルバスタチンを添加し，細胞表面のHLA-DRとβ2GPIの発現およびヒトモノクローナル抗β2GPI依存性抗カルジオリピン抗体（EY2C9）の結合能を解析した．APS自然発症ラットであるenv-pXラットにフルバスタチンを投与し，β2GPI依存性抗カルジオリピン抗体（aCL）を測定した．【結果】HUEhT-1とTHP-1の両細胞表面において，β2GPIの発現およびEY2C9の結合はHLA-DR7発現細胞で亢進していた．フルバスタチンの添加により，HLA-DRとβ2GPIの細胞表面への発現およびEY2C9の結合は抑制され，メバロン酸によりフルバスタチンの作用は拮抗された．またフルバスタチン投与によりenv-pXラットのaCLは有意に低下した．【結語】スタチン製剤はHLA class IIの発現低下を介した自己抗原提示の抑制効果を示すため，APSへの治療効果が予想される．, 日本臨床免疫学会, 日本語

抗C1q抗体は抗リン脂質抗体症候群における補体活性化及び予防治療下の再発に関与する　　　　　　　　　　　　　　　
奥 健志, オルガ・アメングアル, 大村 一将, 中川 育磨, 渡邊 敏之, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本血栓止血学会誌, 25, 2, 243, 243, 2014年04月
(一社)日本血栓止血学会, 日本語

抗リン脂質抗体陽性全身性エリテマトーデスにおけるスタチン初期投与の血栓症発症抑制効果
渡邊 俊之, 奥 健志, Amengual Olga, 中川 育磨, 坊垣 暁之, 保田 晋助, 堀田 哲也, 渥美 達也, 日本血栓止血学会誌, 25, 2, 244, 244, 2014年04月
(一社)日本血栓止血学会, 日本語

抗リン脂質抗体症候群・MCTD ループス腎炎患者における抗リン脂質抗体関連腎症の臨床的特徴についての検討　　　　　　　　　　　　　　　
福井 智子, 保田 晋助, 渡邊 俊之, 秋田 佳奈恵, 大村 一将, 神田 真聡, 中川 育磨, 野口 淳史, 志田 玄貴, 河野 通仁, 清水 裕香, 栗田 崇史, 奥 健志, 坊垣 暁之, オルガ・アメングアル, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 58回, 301, 301, 2014年03月
(一社)日本リウマチ学会, 日本語

抗リン脂質抗体症候群・MCTD 原発性抗リン脂質抗体症候群における血小板減少症は動脈血栓症のリスクと関連する　　　　　　　　　　　　　　　
中川 育磨, 奥 健志, オルガ・アメングアル, 秋田 佳奈恵, 大村 一将, 神田 真聡, 福井 智子, 野口 淳史, 志田 玄貴, 渡邊 俊之, 河野 通仁, 清水 裕香, 栗田 崇史, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 58回, 301, 301, 2014年03月
(一社)日本リウマチ学会, 日本語

SLE スプライシング因子ASF/SF2はSLE患者T細胞におけるRasGRP1スプライシングを制御する
栗田 崇史, 保田 晋助, 河野 通仁, 奥 健志, 坊垣 暁之, Amengual Olga, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 58回, 310, 310, 2014年03月
(一社)日本リウマチ学会, 日本語

SLE 全身性エリテマトーデス患者における動脈硬化の臨床像とリスク因子
渡邊 俊之, 奥 健志, Olga Amengual, 秋田 佳奈恵, 大村 一将, 神田 真聡, 中川 育磨, 野口 淳史, 福井 智子, 志田 玄貴, 河野 通仁, 清水 裕香, 栗田 崇史, 坊垣 暁之, 保田 晋助, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 58回, 360, 360, 2014年03月
(一社)日本リウマチ学会, 日本語

関節リウマチの病因・病態 RasGRP4(Ras guanine nucleotidereleasing protein 4)は関節リウマチ患者の線維芽細胞様滑膜細胞に発現し、その増殖を促進する　　　　　　　　　　　　　　　
河野 通仁, 保田 晋助, 清水 智弘, 栗田 崇史, 奥 健志, 坊垣 暁之, オルガ・アメングアル, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会プログラム・抄録集, 58回, 439, 439, 2014年03月
(一社)日本リウマチ学会, 日本語

慢性関節リウマチ患者から採取した線維芽細胞様滑膜細胞におけるRAsGRP4(Rasグアニンヌクレオチド放出蛋白質4)の滑膜増殖作用
KONO Michihito, YASUDA Shinsuke, SHIMIZU Tomohiro, KURITA Takashi, OKU Kenji, BOHGAKI Toshiyuki, AMENGUAL Olga, HORITA Tetuya, ATSUMI Tatuya, 日本リウマチ学会総会・学術集会プログラム・抄録集, 58th, 2014年

Autoantibodies against component of complement 1 contribute to the complement activation and to the manifestations of refractory antiphospholipid syndrome (APS)
K. Oku, O. Amengual, W. Toshiyuki, K. Yuusaku, F. Yuuichiro, B. Toshiyuki, H. Tetsuya, Y. Shinsuke, A. Tatsuya, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 11, 595, 596, 2013年07月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

THE ANALYSIS OF RISK AND PROTECTIVE FACTORS FOR THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS WITH OR WITHOUT ANTIPHOSPHOLIPID ANTIBODIES
T. Watanabe, K. Oku, O. Amengual, S. Shimamura, I. Nakagawa, A. Noguchi, Y. Kanetsuka, M. Kono, T. Kurita, Y. Fujieda, T. Bohgaki, S. Yasuda, T. Horita, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 72, 482, 482, 2013年06月
BMJ PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

患者由来IgG型モノクローナル抗カルジオリピン/β2-グリコプロテインI抗体の機能と特異性
金塚 雄作, 奥 健志, Amengual Olga, 藤枝 雄一郎, 坊垣 暁之, 堀田 哲也, 保田 晋助, 高田 賢蔵, 渥美 達也, 日本血栓止血学会誌, 24, 2, 229, 229, 2013年04月
(一社)日本血栓止血学会, 日本語

抗リン脂質抗体症候群/MCTD 抗カルジオリピン/β2-グリコプロテインI抗体の多様性 患者由来IgG型モノクローナル抗体を用いた検討
金塚 雄作, 奥 健志, Amengual Olga, 中川 育磨, 渡邊 俊之, 藤枝 雄一郎, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 57回・22回, 334, 334, 2013年03月
(一社)日本リウマチ学会, 日本語

抗リン脂質抗体症候群/MCTD 抗リン脂質抗体症候群における血栓形成機序 向血栓細胞における抗プロトロンビン自己抗体とRibophorinIIの意義
藤枝 雄一郎, 金塚 雄作, 大友 耕太郎, 奥 健志, 坊垣 暁之, Amengual Olga, 堀田 哲也, 保田 晋助, 渥美 達也, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 57回・22回, 334, 334, 2013年03月
(一社)日本リウマチ学会, 日本語

SLE/NPSLE SLE患者T細胞におけるSF2発現レベルの検討
栗田 崇史, 保田 晋助, 河野 通仁, 藤枝 雄一郎, 橋本 陶子, 奥 健志, 坊垣 暁之, Amengual Olga, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 57回・22回, 375, 375, 2013年03月
(一社)日本リウマチ学会, 日本語

SLE/NPSLE 全身性エリテマトーデス患者における血栓症の危険因子に関する検討　　　　　　　　　　　　　　　
渡邊 俊之, 奥 健志, オルガ・アメングアル, 嶋村 抄苗, 中川 育磨, 野口 淳史, 金塚 雄作, 栗田 崇史, 藤枝 雄一郎, 坊垣 暁之, 保田 晋助, 堀田 哲也, 渥美 達也, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 57回・22回, 400, 400, 2013年03月
(一社)日本リウマチ学会, 日本語

関節リウマチの治療 生物学的製剤(TNF阻害薬) インフリキシマブのオンデマンド増量法の長期有用性に関する検討
大友 耕太郎, 金塚 雄作, Amengual Olga, 奥 健志, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 57回・22回, 414, 414, 2013年03月
(一社)日本リウマチ学会, 日本語

β₂-glycoprotein Iと血管新生に関する最近の話題
保田晋助, 藤枝雄一郎, 奥健志, 坊垣暁之, AMENGUAL Olga, 堀田哲也, 渥美達也, 日本血栓止血学会学術標準化委員会シンポジウム, 7th, 2013年

APS患者における抗カルジオリピン-IgG/IgMおよび抗β2グリコプロテインI-IgG/IgM測定の有用性
藤枝 雄一郎, 志田 玄貴, 渡邊 俊之, 金塚 雄作, 奥 健志, 坊垣 暁之, 堀田 哲也, 保田 晋助, Olga Amengual, 渥美 達也, 日本臨床免疫学会会誌, 35, 4, 369, 369, 2012年08月
【背景】抗カルジオリピン抗体(aCL)-IgG/IgM，抗β2-グリコプロテインI (aβ2GPI)-IgG/IgMは抗リン脂質抗体症候群（APS）の診断基準で認められた臨床検査であるが，本邦ではaCL-IgGおよびβ2GPI依存性aCL-IgGのみが保険収載されており，aCL-IgMやaβ2GPI-IgG/IgMを測定する標準化されたアッセイは存在しない．
【目的】aCL-IgG/IgM, aβ2GPI-IgG/IgM測定キット（Phadia: EliA^TM）を用いることによるAPSの診断における有用性を検討した．
【方法】当科外来患者のうち，230例（APS100例，SLE31例，関節リウマチ50例，その他の自己免疫疾患49例）の保存血清を用い，EliA^TMCardiolipin^TM（CL-G, CL-M），EliA^TMβ2-Glycoprotein I（b2-G,b2-M）を測定した．対照として既存のMESACUPカルジオリピン（MESACUP），ヤマサ抗CLβ2GPIキット（ヤマサ）を同時測定した．
【結果】感度，特異度，ROC曲線下面積（AUC）はそれぞれ，CL-G（45%, 94%, 0.80），CL-M（20%, 94%, 0.54），b2-G（33%, 93%, 0.88），b2-M（16%, 99%, 0.64），MESACUP（62%, 94%, 0.81），ヤマサ（51%, 99%, 0.87）であった．CL-G/M, b2-G/Mいずれかが陽性であるときの感度，特異度は55%，88%であり，APS100例でCL-G陰性45例のうち，CL-M, b2-G/Mのいずれかが陽性であるのは10例であった．
【結語】Phadia:EliA^TMの4種類のキットを用いて複数の抗リン脂質抗体検査を組み合わせることで，現行の方法よりもAPS診断の感度をあげることができる．
, 日本臨床免疫学会, 日本語

抗リン脂質抗体症候群の診断における抗リン脂質抗体スコアの有用性と血栓症イベント予測の可能性
大友 耕太郎, 渥美 達也, AMENGUAL Olga, 藤枝 雄一郎, 加藤 将, 奥 健志, 堀田 哲也, 保田 晋助, 小池 隆夫, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 4, 2012年08月01日
日本語

単球系細胞における酸化LDL(APOB)および抗β2GPI抗体によって誘導される組織因子発現の検討
大友耕太郎, 渥美達也, 藤枝雄一郎, 中川久子, 加藤将, AMENGUAL Olga, 近祐次郎, 堀田哲也, 保田晋助, 松本雅記, 畠山鎮次, 小池隆夫, 小池隆夫, 日本血栓止血学会誌, 23, 2, 166, 166, 2012年04月01日
(一社)日本血栓止血学会, 日本語

抗リン脂質抗体症候群/MCTD 抗β2GPI抗体が誘導する組織因子の発現におけるapolipoprotein B100および酸化LDLの役割
大友 耕太郎, 渥美 達也, 藤枝 雄一郎, 中川 久子, 加藤 将, Amengual Olga, 近 祐次郎, 堀田 哲也, 保田 晋助, 小池 隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 56回・21回, 432, 432, 2012年03月
(一社)日本リウマチ学会, 日本語

抗リン脂質抗体症候群/MCTD 抗カルジオリピン抗体および抗β2-グリコプロテインI抗体単独陽性の意義
志田 玄貴, 渥美 達也, 加藤 将, 渡邊 俊之, 河野 通仁, 金塚 雄作, 栗田 崇史, 小谷 俊雄, 藤枝 雄一郎, 大友 耕太郎, 近 祐次郎, 堀田 哲也, 保田 晋助, Amengual Olga, 小池 隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 56回・21回, 432, 432, 2012年03月
(一社)日本リウマチ学会, 日本語

抗リン脂質抗体症候群/MCTD 抗リン脂質抗体症候群患者の動脈血栓症再発予防に関する検討
藤枝 雄一郎, 渥美 達也, 渡邊 俊之, 志田 玄貴, 河野 通仁, 金塚 雄作, 栗田 崇史, 小谷 俊雄, 加藤 将, 大友 耕太郎, Amengual Olga, 近 祐次郎, 堀田 哲也, 保田 晋助, 小池 隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 56回・21回, 433, 433, 2012年03月
(一社)日本リウマチ学会, 日本語

抗リン脂質抗体症候群患者の動脈血栓症再発予防に関する検討
藤枝雄一郎, 渥美達也, 渡邊俊之, 志田玄貴, 河野通仁, 金塚雄作, 栗田崇史, 小谷俊雄, 加藤将, 大友耕太郎, AMENGUAL Olga, 近祐次郎, 堀田哲也, 保田晋助, 小池隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 56th-21st, 2012年

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/Pt) is a useful predictive marker of thrombosis in patients with autoimmune diseases
K. Otomo, O. Amengual, T. Atsumi, Y. Fujieda, M. Kato, T. Horita, S. Yasuda, W. Binder, T. Koike, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 9, 419, 420, 2011年07月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Platelet activation and paradoxical inhibition of ADP induced aggregation by antiphospholipid antibodies in vitro
K. Oku, T. Atsumi, O. Amengual, Y. Fujieda, K. Otomo, M. Kato, S. Furukawa, H. Kitakawa, S. Yasuda, T. Horita, Y. Hori, T. Nishikawa, K. Nihei, M. Ieko, T. Koike, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 9, 165, 165, 2011年07月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

抗リン脂質抗体症候群 抗リン脂質抗体症候群の病態形成におけるCD36の関与
加藤 将, 渥美 達也, 奥 健志, 藤枝 雄一郎, 大友 耕太郎, Amengual Olga, 堀田 哲也, 保田 晋助, 小池 隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 55回・20回, 245, 245, 2011年06月
(一社)日本リウマチ学会, 日本語

欧州各国のTNF阻害薬使用のためのリコメンデーション (特集 世界のリウマチガイドラインをみわたす) -- (各国の治療ガイドライン)
渥美 達也, Amengual Olga, 分子リウマチ治療, 4, 2, 66, 70, 2011年05月
先端医学社, 日本語

抗リン脂質抗体症候群の予後
藤枝雄一郎, 渥美達也, 清水裕香, 河野通仁, 金塚雄作, 栗田崇史, 小谷俊雄, 大友耕太郎, 加藤将, 深谷進司, AMENGUAL Olga, 保田晋助, 堀田哲也, 小池隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 55th-20th, 2011年

本邦における抗リン脂質抗体症候群の予後
藤枝雄一郎, 渥美達也, OLGA Amengual, 加藤将, 大友耕太郎, 奥健志, 片岡浩, 保田晋助, 堀田哲也, 小池隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 54th-19th, 2010年

ホスファチジルセリン依存的アンチプロトロンビン抗体による内皮細胞活性化
OKU Kenji, ATSUMI Tatsuya, MIYAMOTO Eriko, OTOMO Kotaro, KATO Masaru, AMENGUAL Olga, KATAOKA Hiroshi, HORITA Tetsuya, YASUDA Shinsuke, KOIKE Takao, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 53rd-18th, 2009年

ホスファチジルセリン依存性抗プロトロンビン抗体による内皮細胞活性化機序
奥健志, 渥美達也, 宮本江里子, 大友耕太郎, 加藤将, AMENGUAL Olga, 片岡浩, 堀田哲也, 保田晋助, 小池隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 53rd-18th, 2009年

Significance of phospholipid scramblase 1 (PLSCR1) expression on monocytes in patients with antiphospholipid syndrome (APS)　　　　　　　　　　　　　　　
Miyamoto E, Atsumi T, Amengual O, Oku K, Otomo K, Kato M, Kataoka H, Horita T, Yasuda S, Koike T, 52nd Annual General Assembly and Scientific Meeting of Japan College of Rheumatology, Sapporo, Japan, 2008年04月

ホスファチジルセリン依存性抗プロトロンビン抗体による単球活性化機序
奥健志, 渥美達也, AMENGUAL Olga, 片岡浩, 堀田哲也, 保田晋助, 小池隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 52nd-17th, 2008年

The P38 mitogen –activate protein kinase (MAPK) pathway mediates the induction of tissue factor expression by phosphatidylserine dependent monoclonal antiprothrombin antibody with LA activity　　　　　　　　　　　　　　　
Oku K, Atsumi T, Amengual O, Kataoka H, Horita T, Yasuda S, Koike T, American College of Rheumatology 71th National Scientific Meeting, Boston MA , USA, 2007年11月

Phosphatidylserine dependent antiprothrombin antibody induces p38 mitogen-activated protein kinase (MAPK) phosphorylation leading to tissue factor expression
K. Oku, T. Atsumi, O. Amengual, H. Kataoka, T. Horita, S. Yasuda, T. Koike, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 25, 2, 160, 160, 2007年03月
CLINICAL & EXPER RHEUMATOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

In vitro roles of phosphatidylserine dependent antiprothrombin antibody on thrombin generation　　　　　　　　　　　　　　　
Sakai Y, Atsumi T, Amengual O, Yasuda S, Ieko M, Koike T, 5th International Congress of Autoimmunity, Sorrento, Italy, 2006年11月

Induction of Tissue Factor by Monoclonal Phosphatidylserine Dependent Antiprothrombin Antibody
Atsumi T, Amengual O, Sakai Y, Horita T, Yasuda S, Koike T, American College of Rheumatology 69th National Scientific Meeting, San Diego, USA, 52, 9, S599, S600, 2005年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Effects of Phosphatidylserine Dependent Antiprothrombin Antibody on Thrombin Generation In Vitro
Sakai Y, Atsumi T, Amengual O, Yasuda S, Ieko M, Koike T, American College of Rheumatology 69th National Scientific Meeting, San Diego, USA, 52, 9, S599, S599, 2005年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Phosphatidylserine Dependent Antiprothrombin Antibodies Improves the Diagnostic Yield of Antiphospholipid Syndrome　　　　　　　　　　　　　　　
Atsumi T, Amengual O, Ieko M, Sakai Y, Yasuda S, Koike T, 20th Congress of the International Society on Thrombosis and Haemostasis, Sydney, Australia, 2005年08月

Phosphatidylserine dependent antiprothrombin antibodies provide one of the best diagnostic values for the laboratory evaluation in patients with antiphospholipid syndrome.
T Atsumi, M Ieko, Y Sakai, Y Kon, S Furukawa, O Amengual, S Yasuda, Y Amasaki, T Koike, ARTHRITIS AND RHEUMATISM, 50, 9, S68, S69, 2004年09月
WILEY-LISS, 英語, 研究発表ペーパー・要旨（国際会議）

Protective effect of pravastatin on vascular endothelium in patients with systemic sclerosis: A pilot study
S Furukawa, S Yasuda, Y Sakai, M Kondo, Y Kon, O Amengual, Y Amasaki, T Atsumi, T Koike, ARTHRITIS AND RHEUMATISM, 50, 9, S693, S693, 2004年09月
WILEY-LISS, 英語, 研究発表ペーパー・要旨（国際会議）

Diagnostic value of matrix metalloproteinase 3 (MMP-3) in serum of patients with arthralgias
O Amengual, T Atsumi, S Yasuda, Y Amasaki, T Koike, ARTHRITIS AND RHEUMATISM, 50, 9, S161, S162, 2004年09月
WILEY-LISS, 英語, 研究発表ペーパー・要旨（国際会議）

Clinical and immunological manifestations of Japanese patients with antiphospholipid syndrome (APS): A cohort of 82 patients
Y Sakai, T Atsumi, Y Kon, M Bohgaki, S Yasuda, O Amengual, Y Amasaki, T Koike, THROMBOSIS RESEARCH, 114, 5-6, 663, 664, 2004年
PERGAMON-ELSEVIER SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

The value of IGM phosphatidylserine dependent antiprothrombin antibody determination for the diagnosis of antiphospholipid syndrome
O Amengual, T Atsumi, K Yujiro, Y Sakai, M Bohgaki, S Furukawa, S Yasuda, Y Amasaki, M Ieko, T Koike, THROMBOSIS RESEARCH, 114, 5-6, 671, 672, 2004年
PERGAMON-ELSEVIER SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

The human platelet antigen 6Wb represents a risk factor for thrombocytopenia in patients with systemic lupus erythernatosus.
O Amengual, T Atsumi, Y Komano, S Jodo, Y Amasaki, K Ichikawa, T Koike, ARTHRITIS AND RHEUMATISM, 46, 9, S442, S442, 2002年09月
WILEY-LISS, 英語, 研究発表ペーパー・要旨（国際会議）

Clinical significance of IgA anticardiolipin antibody in patients with systemic lupus erythematosus　　　　　　　　　　　　　　　
Bertolaccini ML, Atsumi T, Amengual O, Katsumata K, Khamashta MA, Hughes GRV, 6th International Lupus Conference. Barcelona, Spain, 2001年03月

Apolipoprotein(a) deposition in atherosclerotic coronary arteries of a patient with systemic lupus erythematosus: comment on the article by Romero et al - Reply
T Atsumi, O Amengual, MA Khamashta, FI Romero, GRV Hughes, ARTHRITIS AND RHEUMATISM, 43, 9, 2142, 2142, 2000年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 速報，短報，研究ノート等（学術雑誌）

Low frequency of IgA anticardiolipin antibody in patients with systemic lupus erythematosus.
ML Bertolaccini, T Atsumi, O Amengual, K Katsumata, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 43, 9, S256, S256, 2000年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Deletion type of angiotensin 1-converting enzyme gene was not an additional risk factor for arterial thrombosis in patients with antiphospholipid syndrome.
K Katsumata, T Atsumi, ML Sanchez, FI Romero, ML Bertolaccini, A Funke, O Amengual, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 42, 9, S368, S368, 1999年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Autoantibodies against oxdized lipoprotein (a) in systemic lupus erthematosus (SLE).
F Romero, MA Khamashta, T Atsumi, FJ Tinahones, JM Gomez-Zumaquero, O Amengual, K Katsumata, ML Sanchez, G Swana, GRV Hughes, ARTHRITIS AND RHEUMATISM, 42, 9, S147, S147, 1999年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Anticardiolipin antibodies in scleroderma and mixed connective tissue disease are not dependent on the cofactor b2-glycoprotein I neither associated with the antiphospholipid syndrome.　　　　　　　　　　　　　　　
Mendonca L, Amengual O, Bertolaccini ML, Atsumi T, Khamashta MA, Hughes GRV, Second International Congress on Autoimmunity, Tel Aviv, Israel,, 1999年03月

Clinical characteristics of anticardiolipin antibody positive patients with systemic lupus erythematosus　　　　　　　　　　　　　　　
Sanfilippo SS, Bertolaccini ML, Amengual O, Atsumi T, Khamashta MA, D ́Cruz D, Amft N, Swana GT, Hughes GRV, American College of Rheumatology 62nd National Scientific Meeting, San Diego, USA, 1998年11月

Mendonça LLF, Amengual O, Bertolaccini ML, Atsumi T, Khamashta MA, Hughes GRV
Mendonça LLF, Amengual O, Bertolaccini ML, Atsumi T, Khamashta MA, Hughes GRV, American College of Rheumatology 62nd National Scientific Meeting, San Diego, USA, 41, 9, S167, S167, 1998年11月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Correlation between b2-glycoprotein I (b 2GPI) valine/leucin247 polymorphism and antib2GPI antibodies in patients with primary antiphospholipid syndrome.
Atsumi T, Tsutsumi A, Amengual O, Khamashta MA, Hughes GRV, Miyoshi Y, Ichikawa K, Koike T, American College of Rheumatology 62nd National Scientific Meeting, San Diego, USA, 41, 9, S240, S240, 1998年11月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

IgA anticardiolipin antibody testing does not further contribute to the diagnosis of systemic lupus erythematosus.　　　　　　　　　　　　　　　
Bertolaccini ML, Atsumi T, Amengual O, Katsumata K, Khamashta MA, Hughes GRV, The 8th International Symposium on Antiphospholipid Antibodies, Sapporo Japan, 1998年10月

Genetics of antiphospholipid syndrome: b2-glycoprotein I (b2GPI) valine/leucin247 polymorphism and antib2GPI antibodies in patients with primary antiphospholipid syndrome.　　　　　　　　　　　　　　　
Atsumi T, Tsutsumi A, Amengual O, Khamashta MA, Hughes GRV, Miyoshi Y, Ichikawa K, Koike T, The 8th International Symposium on Antiphospholipid Antibodies, Sapporo Japan, 1998年10月

Antiphosphatidylethanolamine is not a marker for antiphospholipid syndrome in patients with systemic lupus erythematosus.　　　　　　　　　　　　　　　
Bertolaccini ML, Amengual O, Atsumi T, Roch B, Khamashta MA, Hughes GRV, The 8th International Symposium on Antiphospholipid Antibodies, Sapporo Japan, 1998年10月

Antibodies to human prothrombin (aPT): prevalence and clinical significance in patients with antiphospholipid syndrome (APS).　　　　　　　　　　　　　　　
Bertolaccini ML, Atsumi T, Amengual O, Khamashta MA, Hughes GRV, The 8th International Symposium on Antiphospholipid Antibodies, Sapporo Japan, 1998年10月

Clinical characteristics of anticardiolipin antibody positive patients with systemic lupus erythematosus.
Sanfilippo SS, Bertolaccini ML, Amengual O, Atsumi T, Khamashta MA, D ́Cruz D, Amft N, Swana GT, Hughes GRV, The 8th International Symposium on Antiphospholipid Antibodies, Sapporo Japan, 41, 9, S241, S241, 1998年10月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

IgG2 restriction of anti beta 2 glycoprotein I antibodies in patients with antiphospholipid syndrome.
O Amengual, T Atsumi, MA Khamashta, ML Bertolaccini, GRV Hughes, ARTHRITIS AND RHEUMATISM, 41, 9, S167, S167, 1998年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Autoantibodies to prothrombin-phosphatidylserine complex: Clinical significance in systemic lupus erythematosus.
A Funke, ML Bertolaccini, T Atsumi, O Amengual, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 41, 9, S240, S240, 1998年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Prothrombin mutation is not associated with thrombosis in patients with antiphospholipid syndrome.
ML Bertolaccini, T Atsumi, BJ Hunt, O Amengual, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 41, 9, S170, S170, 1998年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Elevated frequency of tumor necrosis factor alfa (TNF alpha) promoter polymorphism TNF238-A in patients with antiphospholipid syndrome (APS).
ML Bertolaccini, T Atsumi, AR Caliz, O Amengual, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 41, 9, S240, S240, 1998年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

HLA-DM polymorphisms and antiphospholipid antibodies
ML Sanchez, K Katsumata, T Atsumi, FI Romero, ML Bertolaccini, A Funke, O Amengual, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 41, 9, S172, S172, 1998年09月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Anti-cardiolipin antibodies in mixed connective tissue disease (MCTD) are b2 glycoprotein I independent and not associated with antiphospholipid syndrome (APS).　　　　　　　　　　　　　　　
Mendonça LLF, Amengual O, Atsumi T, Yoshinari NH, Khamashta MA, Hughes GRV, Symposium in Systemic Lupus Erythematosus, Cancún, México, 1998年05月

Most anticardiolipin antibodies in mixed connective tissue disease are beta(2)-glycoprotein independent
LLF Mendonca, O Amengual, T Atsumi, MA Khamashta, GRV Hughes, JOURNAL OF RHEUMATOLOGY, 25, 1, 189, 190, 1998年01月
J RHEUMATOL PUBL CO, 英語, 速報，短報，研究ノート等（学術雑誌）

Association of antibodies against beta2-glycoprotein I (2GPI) antibody and oxidized low-density lipoprotein (ox-LDL) to arterial disease in systemic lupus erythematosus (SLE).
Romero F, Amengual O, Atsumi T, Khamashta MA, Bertolaccini L, Tinahones F, Hughes GRV, American College of Rheumatology 61st National Scientific Meeting. Washington, USA, 40, 9, 1642, 1642, 1997年11月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Increase frequency of factor V Leiden mutation in 158 patients with antiphospholipid antibodies.
AR Caliz, IL Pablos, PE Carreira, T Atsumi, L Serrano, O Amengual, B Santiago, MA Khamashta, GomezReino, II, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 1605, 1605, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Induction of tissue factor expression by antiphospholipid antibodies.
O Amengual, T Atsumi, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 1698, 1698, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Autoantibodies to human prothrombin (aPT) and clinical manifestations in 207 systemic lupus erythematosus (SLE).
ML Bertolaccini, T Atsumi, MA Khamashta, O Amengual, FL Romero, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 1702, 1702, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Arterial disease and thrombosis in the antiphospholipid syndrome (APS): A pathogenic role for endothelin-1 (ET-1)
T Atsumi, MA Khamashta, RS Haworth, G Brooks, O Amengual, K Ichikawa, T Koike, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 1602, 1602, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

No correlation between Fc gamma RIIA H/R-131 polymorphism and clinical manifestations of antiphospholipid syndrome (APS).
AR Caliz, T Atsumi, MA Khamashta, O Amengual, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 1606, 1606, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Multiple antiphospholipid tests do not increase the diagnostic yield in antiphospholipid syndrome (APS).
B Roch, MA Khamashta, T Atsumi, ML Bertolaccini, O Amengual, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 1617, 1617, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Association of primary antiphospholipid syndrome and anti-beta2-glycoprotein I antibodies with the HLA DRB1*1302
AR Caliz, T Atsumi, E Kondeatis, MA Khamashta, O Amengual, S Knights, RV Vaughan, JS Lanchbury, GRV Hughes, ARTHRITIS AND RHEUMATISM, 40, 9, 440, 440, 1997年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Anti beta2- glycoprotein I (b2GPI) antibody and anti oxidized low-density lipoprotein (ox-LDL) antibody in patients with systemic lupus erythematosus (SLE).　　　　　　　　　　　　　　　
Romero F, Amengual O, Atsumi T, Khamashta MA, Bertolaccini L, Tinahones F, Hughes GRV, Annual General Meeting of the British Society for Rheumatology, Harrogate, UK, 1997年

Beta 2-Glycoprotein I dependent "anti protein C" antibodies in antiphospholipid syndrome.　　　　　　　　　　　　　　　
Atsumi T, Khamashta MA, Amengual O, Donohoe S, Mackie I, Hughes GRV, American College of Rheumatology 60th National Scientific Meeting. Orlando, USA,, 1996年10月

High plasma levels of lipoprotein (a) in patients with primary and secondary antiphospholipid syndrome.
MI Leandro, T Atsumi, M Khamashta, C Andujar, O Amengual, GRV Hughes, ARTHRITIS AND RHEUMATISM, 39, 9, 419, 419, 1996年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Antibodies against oxidized low-density lipoprotein (ox-LDL) in 107 patients with antiphospholipid syndrome (APS).
O Amengual, T Atsumi, MA Khamashta, F Tinaones, MJ Cuadrado, GRV Hughes, ARTHRITIS AND RHEUMATISM, 39, 9, 420, 420, 1996年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Beta2-glycoprotein I (beta 2GPI) dependent ''anti protein C'' antibody in antiphospholipid syndrome (APS).
T Atsumi, MA Khamashta, O Amengual, S Donohoe, Mackie, I, GRV Hughes, ARTHRITIS AND RHEUMATISM, 39, 9, 397, 397, 1996年09月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Increased plasma level of tissue factor (TF) in patients with antiphospholipid syndrome (APS).
O Amengual, T Atsumi, MA Khamashta, GRV Hughes, ARTHRITIS AND RHEUMATISM, 39, 9, 421, 421, 1996年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Beta 2-glymprotein I (beta 2-GPI) antibody specificity in patients with the antiphospholipid syndrome (APS)
O Amengual, T Atsumi, M Khamashta, T Koike, GRV Hughes, BRITISH JOURNAL OF HAEMATOLOGY, 93, 1200, 1200, 1996年06月
BLACKWELL SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Anticardiolipin and antib2 glycoprotein I antibodies are no associated with antiphospholipid syndrome (APS) in mixed connective tissue diseases (MCTD).　　　　　　　　　　　　　　　
Mendonça LLF, Amengual O, Atsumi T, Yoshinari NH, Souza FV, MA Khamashta MA, Hughes GRV, Annual General Meeting of the British Society for Rheumatology, Harrogate, UK, 1996年

Binding of anticardiolipin antibody to protein C with beta 2-Glycoprotein I and cardiolipin
Atsumi T, Khamashta MA, Amengual O, Ichikawa K, Koike T, Hughes GRV, Second Meeting of the European Haematology Association. Paris, France,, 93, 1199, 1199, 1996年
BLACKWELL SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

SPECIFICITY OF ELISA FOR ANTIBODY TO BETA-2-GLYCOPROTEIN-I (BETA-2-GPI) IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME (APS)
O AMENGUAL, T ATSUMI, M KHAMASHTA, GRV HUGHES, ARTHRITIS AND RHEUMATISM, 38, 9, 109, 109, 1995年09月
LIPPINCOTT-RAVEN PUBL, 英語, 研究発表ペーパー・要旨（国際会議）

Relapsing polychondritis, clinical manifestations and evolution of six cases.　　　　　　　　　　　　　　　
Garmendia ES, Amengual O, Román E, Navío T, Brito E, The Annual Meeting of the Spanish Society of Rheumatology, Sevilla, Spain, 1994年05月

Efficacy and safety of Cyclosporin in the treatment of unresponsive childhood autoimmune rheumatic diseases.　　　　　　　　　　　　　　　
Gamir ML, Amengual O, Román E, Navío T, Revenga M, Garmendia ES, 2nd European Conference on Paediatric Rheumatology.,Pavia, Italy, 1994年

Soft tissue calcification in systemic lupus erythematosus.　　　　　　　　　　　　　　　
López Meseguer A, Amengual O, Ferreira A, Zea A, Orte, J, he Annual Meeting of the Spanish Society of Rheumatology, San Sebastián, Spain, 1992年05月

Pathogenesis of antiphospholipid syndrome. In Systemic lupus erythematosus, basic, applied and clinical aspects.　　　　　　　　　　　　　　　
Olga Amengual, Tatssuya Atsumi, Edited by George C Tsokos. Chapter 56
Academic Press, 2020年, ［分担執筆］

Women and Science. (In Spanish)　　　　　　　　　　　　　　　
García-Martín F, Rosich M, de Vega S, San Gabriel A, Amengual O
Journal of Science and Humanities Fundación Areces., 2018年07月, ［分担執筆］

Clinical and Prognostic Significance of Non-criteria Antiphospholipid Antibody Tests. In Antiphospholipid Syndrome: Current Research Highlights and Clinical Insights.　　　　　　　　　　　　　　　
Bertolaccin ML, Amengual O, Artim-Eser B, Atsumi T, de Groot PG, de Laat, B, Devreese K, Giles I, Meroni PL, Borghi MO, Rahman A, Rand J, Regnault V, Kumar R, Tincani A, Wahl D, Willis R, Zuily S, Sanna G, Edited by Doruk Erkan and Dr. Michael Lockshin.
Springer International Publishing, 2017年, ［分担執筆］

Disease and Risk Measurement Criteria in APS. Antiphospholipid score. In Antiphospholipid Syndrome: Current Research Highlights and Clinical Insights.　　　　　　　　　　　　　　　
Amigo MC, Oku K, Sciascia S, Goycoechea-Robles MV, Zuily S, Amengual O, Roccatello D, Otomo K, Atsumi T, Bertolaccini ML, Wahl D, Edited by Doruk Erkan and Dr. Michael Lockshin.
Publisher Springer International Publishing, 2017年, ［分担執筆］

Laboratory Markers with clinical significance in the antiphospholipid Syndrome.In: Cervera R, Khamashta MA, editors Antiphospholipid Syndrome in Systemic Autoimmune Diseases　　　　　　　　　　　　　　　
アメングアル オルガ Bertolaccini ML, Atsumi T
Elsevier, 2016年, ［その他］

Pathogenesis of antiphospholipid syndrome. In: George C Tsokos, editor.Systemic lupus erythematosus, basic, applied and clinical aspects　　　　　　　　　　　　　　　
アメングアル オルガ, Tatsuya Atsumi
Academic Press, 2016年

Task Force Report on “Non-criteria” Antiphospholipid Antibodies　　　　　　　　　　　　　　　
アメングアル オルガ
Springer, 2012年, ［その他］

Antiphospholipid syndrome pathogenesis.In: Lahita RG, editor. Systemic Lupus Erythematosus, 5th edition.　　　　　　　　　　　　　　　
Atsumi T, Amengual O, Koike T
San Diego: Academic Press, 2010年

Ethiopathology of the antiphospholipid syndrome.In: Tanaka K and Davie EW editors. Recent Advances in Thrombosis and Haemostasis　　　　　　　　　　　　　　　
Atsumi T, Amengual O, Koike T, In: Tanaka K and Davie EW editors. Recent Advances in Thrombosis and Haemostasis
Springer Japan KK, 2008年

Antiphospholipid antibodies and the antiphospholipid syndrome.In: New Innmunology Research Developments　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Koike T, In: New Innmunology Research Developments
Nova Publishers, Inc, 2008年

Genetics of antiphospholipid syndrome.In: Khamashta MA editor. Hughes Syndrome: Antiphospholipid syndrome, 2nd edition　　　　　　　　　　　　　　　
Atsumi T, Amengual O, In: Khamashta MA editor. Hughes Syndrome: Antiphospholipid syndrome, 2nd edition
London Springer-Verlag ,, 2006年

Antiphospholipid syndrome and atherosclerosis. In: Atherosclerosis and Autoimmunity. Y Shoenfeld, D Harats and G. Wick editors,　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
Elseviere Science B.V, 2001年

"Endotheliology” in antiphospholipid antibodies. In: Atherosclerosis and Autoimmunity. Y Shoenfeld , D Harats and G. Wick editors.　　　　　　　　　　　　　　　
Atsumi T, Amengual O, Khamashta MA
Elseviere Science B.V., 2001年

Antiprothombin antibodies. In: Khamashta MA editor. Hughes Syndrome　　　　　　　　　　　　　　　
Bertolaccini ML, Amengual O, Atsumi T
London Springer;, 2000年

Los anticoagulantes y antiagregantes plaquetarios. In: Manual de inflamación　　　　　　　　　　　　　　　
Cuadrado MJ, Amengual O
Medical & Marketing Communications SL. Madrid, 1999年

魚の摂取量が関節リウマチ患者の分子標的治療に与える影響に関する研究　　　　　　　　　　　　　　　
垂水 政人, アメングアルオルガ, 藤枝雄一郎, 安田允孝, 小住由依, 竹山脩平, 吉村大, 久田諒, 河野 通仁, 加藤 将, 渥美 達也
日本臨床リウマチ学会, 札幌, 2022年10月, 日本語, 口頭発表（一般）

Advances in the management of Rheumatoid Arthritis　　　　　　　　　　　　　　　
Olga Amengual
School of Pharmaceutical Sciences, Fukuoka, Japan., 2022年06月20日
［招待講演］

Intake of fish rich in n-3 polyunsaturated fatty acids is associated with good response to treatment in rheumatoid arthritis patients receiving targeted therapies　　　　　　　　　　　　　　　
Tarumi M, Amengual O, Fujieda Y, Navidad Fuentes M, Tsuchida N, Yasuda M, Nishino K, Kosumi Y, Takeyama S, Yoshimura M, Ninagawa K, Aso K, Kono M, Kato M, Cáliz Cáliz R, Atsumi T
The Annual European Congress of Rheumatology (EULAR), 2022年06月, 英語, その他
2022年06月01日 - 2022年06月04日

抗リン脂質症候群国際共同研究プロジェクト　　　　　　　　　　　　　　　
Olga Amengual
第16回日本血栓止血学会学術標準化委員会シンポジウム, 2022年02月19日, 口頭発表（招待・特別）
［招待講演］

Rheumatology and the Spectrum of rheumatic diseases　　　　　　　　　　　　　　　
School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, 2022年01月20日
［招待講演］

Advances in the treatment of Rheumatoid Arthritis　　　　　　　　　　　　　　　
Olga Amengual
School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 2021年07月12日, 英語
［招待講演］

What is Rheumatology? Rheumatology in the healthcare system　　　　　　　　　　　　　　　
the School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, 2020年07月03日, 英語
［招待講演］

Prophylaxis for the prevention of obstetric complications in asymptomatic women with antiphospholipid antibodies.　　　　　　　　　　　　　　　
Amengual O, Fujita D, Otta E, Carmona L, Kenji O, Sugiura-Ogasawara M, Murashima A, Atsumi T
The Annual European Congress of Rheumatology EULAR, Rome, Italy, 2020年06月, 英語, 口頭発表（一般）

Measures to prevent COVID-19 infection　　　　　　　　　　　　　　　
Olga Amengual
Webinar entitled “What we are learning about covid-19 combined experiences from Japan and Spain” organized by the Association of Spanish Researchers in Japan (ACE Japón), 2020年04月24日
［招待講演］

Effects of fish consumption on response to targeted therapies in Japanese and Spanish rheumatoid arthritis patients.　　　　　　　　　　　　　　　
Amengual O, Caliz R
超異分野 meetup -Toward innovation beyond boundaries. Organized by Hokkaido Diversity Research Environment Promotion Network., 2020年03月04日, 英語, ポスター発表

Long-term effect of a medical English course on communication abilities of graduate medical students.　　　　　　　　　　　　　　　
Amengual O, Fujieda Y, Oku K, Atsumi T
Asia Pacific Medical Education Conference (APMEC), Singapore, 2020年01月, 英語, 口頭発表（一般）
2020年01月08日 - 2020年01月12日

Clinical significance of antiphospholipid antibodies and management of the antiphospholipid syndrome　　　　　　　　　　　　　　　
Olga Amengual
Inter-hospital clinical session for hospitals in the region of Andalucía held at the Hospital Virgen de la Nieves,Granada. Spain, 2020年, 口頭発表（招待・特別）
［招待講演］

What is Rheumatology? Importance in the health system　　　　　　　　　　　　　　　
Olga Amengual
Sapporo English Medical Interpreters' (SEMI) Group, 2019年12月06日, 英語, 口頭発表（招待・特別）
［招待講演］

International collaborative approach in the antiphospholipid syndrome　　　　　　　　　　　　　　　
Olga Amengual
Second meeting of the Association of Spanish Researchers in Japan (ACE Japón), ). Okinawa OIST,, 2019年11月, 英語, 口頭発表（一般）
2019年11月28日 - 2019年11月28日

IgG phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome　　　　　　　　　　　　　　　
Amengual O, Sugiura-Ogasawara M, Oku K, Murashima A, Atsumi T
第44回日本臨床免疫学会総会 運営事務局. 東京, 2019年09月08日, 英語

Sapporo, the city of Antiphospholipid Syndrome　　　　　　　　　　　　　　　
Olga Amengual
First meeting of the Association of Spanish Researchers in Japan ( ACE Japan). Tokyo, Japan, 2018年11月10日, 英語, 口頭発表（一般）

Longitudinal evolution of IgM phosphatidylserine-dependent antiprothrombin antibody titers in patients with autoimmune diseases.　　　　　　　　　　　　　　　
Amengual O, Nakamura H, Oku K, Hisada R, Fujieda Y, Kato M, Bohgaki T, Yasuda S, Atsumi T
The 10th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis, Sapporo, Japan, 2018年06月, 英語, ポスター発表

Clinical relevance of testing IgM phosphatidylserine dependent antiprothrombin antibodies.　　　　　　　　　　　　　　　
Amengual O, Nakamura H, Oku K, Hisada R, Fujieda Y, Kato M, Bohgaki T, Yasuda S, Atsumi T
The 10th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis, Sapporo, Japan, 2018年, 英語, 口頭発表（一般）

Pain and stiffness in pelvic girdle, a case discussion.　　　　　　　　　　　　　　　
アメングアル オルガ
リウマチ・膠原病診療のピットフォール. Sapporo, Japan, 2017年09月06日, 英語
［招待講演］

抗リン脂質症候群の診断のためのIgGホスファチジルセリン依存性抗プロトロンビン抗体検査。　　　　　　　　　　　　　　　
Amengual O, Sugiura-Ogasawara M, Oku K, Murashima A, Atsumi T
第;回日本臨床免疫学会総会;運営事務局, 2017年09月

大学院生に対する卒後医学英語教育の試みとプライマリ・ケア領域への医学英語教育の提言　　　　　　　　　　　　　　　
Olga Amengual, Manabu Murakami, Toshiyuki Bohgaki , Kenji Oku, Tatsuya Atsumi.
y Care Allied Studies., 2016年07月02日, 口頭発表（一般）

学部生に対する卒前医学英語教育の試みとプライマリ・ケア領域への医学英語教育の提言　　　　　　　　　　　　　　　
Olga Amengual, Manabu Murakami, Toshiyuki Bohgaki, Kenji Oku, Tatsuya Atsumi
日本プライマリ・ケア連合学会北海道ブロック支部第4回地方会, 2016年07月02日, 口頭発表（一般）

Women Physicians in Europe: Career & Family Balance.　　　　　　　　　　　　　　　
アメングアル オルガ
医学生研究修医と語る会.Hokkaido Medical Association Hokkaido. Sapporo, Japan, 2016年02月29日, 英語
［招待講演］

Why Rheumatology is important in the health care system?　　　　　　　　　　　　　　　
アメングアル オルガ
Takikawa City Hospital, Hokkaido Japan, 2015年11月18日, 英語
［招待講演］

医学部大学院生のコミュニケーション能力における医学英語プログラムの効果。　　　　　　　　　　　　　　　
Olga Amengual, Murakami M, Jego EH, Bohgaki T, Oku K, Otaki J, Atsumi T
The Annual Meeting of the Spanish Society for medical Education. Murcia, Spain, 2015年10月, 口頭発表（一般）
2015年10月28日 - 2015年10月31日

医療英語講座が医学生のコミュニケーション能力に与える影響　　　　　　　　　　　　　　　
Amengual O, Murakami M, Jego EH, Bohgaki T, Oku K, Otaki J
The 47th Annual Meeting of the Japan Society for medical Education. Niigata, Japan, 2015年07月, ポスター発表
2015年07月24日 - 2015年07月25日

Prophylaxis for the prevention of obstetric complications in asymptomatic women with antiphospholipid antibodies　　　　　　　　　　　　　　　
Amengual O, Fujita D, Otta E, Carmona L, Kenji O, Sugiura-Ogasawara M, Murashima A, Atsumi T
The Annual European Congress of Rheumatology EULAR, Rome, Italy, 2015年06月, 英語, 口頭発表（一般）

Significance of IgG phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results from the initial and validation studies.　　　　　　　　　　　　　　　
Amengual O, Forastiero R, Sugiura-Ogasawara M, Oku K, Otomo K, Alves J, C. Favas C, Zigon P, Ambrozic A, Tomšic M, Ruiz-Irastorza G, Ruiz-Arruza I, Bertolaccini ML, Norman GL, Shums Z, Arai J
The Annual European Congress of Rheumatology EULAR, Rome, Italy, 2015年06月, 英語, 口頭発表（一般）

International Multi-centre study to evaluate the clinical significance of phosphatidylserine-dependent antiprothrombin antibodies o the diagnosis of antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Forastiero R, Sugiura-Ogasawara M, Oku K, Otomo K, Alves J, C. Favas C, Zigon P, Ambrozic A, Tomšic M, Ruiz-Irastorza G, Ruiz-Arruza I, Bertolaccini ML, Norman GL, Shums Z, Arai J, Atsumi T
European League Against Rheumatism, EULAR, Paris, France, 2014年06月, 英語, ポスター発表

What is a systematic review?　　　　　　　　　　　　　　　
Olga Amengual
Ten Topics in Rheumatology, 2012年09月01日, スペイン語
［招待講演］

A comparative analysis of the methods to detect phosphatidylserine-dependent antiprothrombin antibodies.　　　　　　　　　　　　　　　
Olga Amengual
6th Annual Congress of Asia Pacific Society on Thrombosis and Haemostasis, Bali, Indonesis, 2010年10月

A comparative analysis of the methods to detect phosphatidylserine-dependent antiprothrombin antibodies　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Binder W, Arai J, Kato M, Otomo K, Fujieda Y, Horital T, Yasuda S, Takao K
6th Annual Congress of Asia Pacific Society on Thrombosis and Haemostasis. Bali, Indonesia, 2010年10月, 英語, 口頭発表（一般）

Up-regulated expression of Phospholipid Scramblase 1 in antiphospholipid syndrome: a novel pathogenic mechanism of thrombosis.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Suzuki E, Oku K, Kato M, Otomo K, Fujieda Y, Kataoka H, Horita T, Yasuda S, Koike T
7th International Congress on Autoimmunity Ljubljana, Slovenia, 2010年05月, 英語, 口頭発表（一般）

Up-regulated expression of Phospholipid Scramblase 1 on monocytes in patients with antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Suzuki E, Oku K, Hashimoto T, Kato M, Otomo K, Fujieda Y, Kataoka H, Horita T, Yasuda S, Koike T
American College of Rheumatology 73rd Annual Scientific Meeting, Philadelphia, USA, October, 2009年10月

Aminophospholipid translocase (ATP10A) polymorphisms and the risk of thrombosis in patients with antiphospholipid antibodies.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Horita T, Kataoka H, Yasuda S, Koike T
American College of Rheumatology 71th National Scientific Meeting, Boston MA, USA, 2007年11月

Beta2glycoprotein I-dependent anticardiolipin antibodies-induced tissue factor expression is enhanced by interferon alpha; a crucial role for lipid scramblase 1.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Kataoka H, Horita T, Yasuda S, Koike T
American College of Rheumatology 70th National Scientific Meeting, Washington DC, USA, 2006年11月

The role of;lipid;scramblase;in the induction of;issue;factor mediated by bet;lycoprotein I-dependent anticardiolipin antibodies　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Oku K, Kataoka H, Horita T, Yasuda S, Koike T
5th International Congress of Autoimmunity, Sorrento, Italy, 2006年11月

Induction of Lipid Scramblase mRNA by Antiphosphospholip Antibodies: A New Possible Pathogenic Mechanism of Thrombosis in Patients with Antiphospholipid Syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Sakai Y, Tetsuya H, Shinsuke Y, Takao K
American College of Rheumatology 69th National Scientific Meeting, San Diego, USA, 2005年11月

The value of IgM phosphatidylserine dependent antiprothrombin antibody determination for the diagnosis of antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Kon Y, Sakai Y, Bohgaki M, Furukawa S, Yasuda S, Amasaki Y, Ieko M, Koike T
11th International Congress on Antiphospholipid Antibodies. Sydney, Australia,, 2004年11月

Diagnostic value of matrix metalloproteinase 3 (MMP-3) in serum of patients with arthralgias.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Yasuda S, Amasaki Y, Koike T
American College of Rheumatology 68th National Scientific Meeting, San Antonio, USA, 2004年10月

The determination of IgM phosphatidylserine dependent antiprothrombin antibodies is a useful tool for the evaluation of patients with lupus anticoagulant　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Kon Y, Sakai Y, Furukawa S, Yasuda S, Jodo S, Amasaki Y, Koike T
7th International Congress SLE and related conditions. New York, USA, 2004年05月

Diagnostic value of matrix metalloproteinase-3 (MMP-3) serum levels in rheumatoid arthritis (RA)　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Jodo S, Amasaki Y, Koike T
48th General Assembly and Scientific Meeting of Japan College of Rheumatology, Okayama, Japan, 2004年04月

The human platelet antigen 6Wb represents a risk factor for thrombosis in patients with systemic lupus erythematosus.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Komano Y, Jodo S, Amasaki Y, Ichikawa K, Koike T
American College of Rheumatology 66th National Scientific Meeting. New Orleans, USA, 2002年10月

Glycoprotein IIIA polymorphism HPA6Wa/b and aPL are independent risks for thrombocytopenia in patients with SLE. 10th International Symposium on Antiphospholipid Antibodies　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Komano Y, Jodo S, Amasaki Y, Ichikawa K, Koike T
Taormina, Italy,, 2002年09月

Update in the antiphospholipid syndrome　　　　　　　　　　　　　　　
Olga Amengual
Annual Meeting of the Spanish Society of Immunology, 2002年06月14日
［招待講演］

Sindrome antifosfolipido　　　　　　　　　　　　　　　
Olga Amengual
Meeting of the Extremena Society of Rheumatology, Caceres, Spain, 2000年

IgG2 restriction of anti2 Glycoprotein I antibodies in patients with antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Bertolaccini ML, Hughes GRV
American College of Rheumatology 62nd National Scientific Meeting, San Diego, USA, 1998年11月

IgG2 restriction of anti2 Glycoprotein I antibodies in patients with antiphospholipid syndrome　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Bertolaccini ML, Hughes GRV
The 8th International Symposium on Antiphospholipid Antibodies, Sapporo Japan, 1998年10月

Thrombotic mechanisms in autoimmune diseases　　　　　　　　　　　　　　　
Olga Amengual
Ten Topics , Barcelona, Spain, 1998年07月, 英語

Restriction of anti-2 glycoprotein I antibodies to the IgG2 subclass in patients with antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Bertolaccini ML, Hughes GRV
Annual Meeting of the Spanish Society of Rheumatology, Cádiz, Spain, 1998年05月, スペイン語, 口頭発表（一般）

Induction of tissue factor expression by antiphospholipid antibodies.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
American College of Rheumatology 61st National Scientific Meeting. Washington,USA,, 1997年11月, 口頭発表（一般）

Up-regulation of tissue factor (TF) in patients with antiphospholipid syndrome (APS)　　　　　　　　　　　　　　　
Amengual, O, Atsumi T, Khamashta MA, Hughes GRV
Annual General Meeting of the British Society for Rheumatology, Harrogate, UK, 1997年

Increased plasma levels of tissue factor in patients with antiphospholipid syndrome　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
American College of Rheumatology 60th National Scientific Meeting. Orlando, USA, 1996年10月

Antibodies against oxidized low-density lipoprotein in 107 patients with antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Tinahones F, Cuadrado MJ, Hughes GRV
American College of Rheumatology 60th National Scientific Meeting. Orlando, USA, 1996年10月

Increased plasma levels of tissue factor in patients with antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
7th International Symposium on Antiphospholipid Antibodies. New Orleans, Louisiana, USA, 1996年10月

Clinical significance of antiphospholpid antibody family　　　　　　　　　　　　　　　
Olga Amengual
Anual Meeting of the SORCOM, Madrid, Spain, 1996年06月

Beta 2-glycoprotein I antibody specificity in patients with the antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
Annual General Meeting of the British Society for Rheumatology. Brighton, UK, 1996年

Beta 2-glycoprotein I antibody specificity in patients with the antiphospholipid syndrome　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
Second Meeting of the European Haematology Association. Paris, France, 1996年

Thrombosis and antiphospholipid antibodies　　　　　　　　　　　　　　　
Olga Amengual
Multidisciplinary Simposium on systemic lupus eryhtematosus, Hospital Juan Ramón Jiménez, Huelva,Spain, 1995年11月, 英語

Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome.　　　　　　　　　　　　　　　
Amengual O, Atsumi T, Khamashta MA, Hughes GRV
American College of Rheumatology 59th National Scientific Meeting. San Francisco, USA, 1995年10月

Cyclosporine therapy in autoimmune rheumatological diseases of childhood.　　　　　　　　　　　　　　　
Amengual O, Gamir ML, Román E, Navío T, Revenga M, Garmendia EE
The Annual Meeting of the Spanish Society of Rheumatology, Sevilla, Spain, 1994年05月, スペイン語

Coordinator and Lecturer of English Medical Program　　　　　　　　　　　　　　　
Department of Rheumatology, Endocrinology and Neprology, Hokkaido University Gradutate School of Medicine)
2012年04月 - 現在

(専門英語) 講座の講師　　　　　　　　　　　　　　　
School of Pharmaceutical Sciences, Fukuoka, Japan
2022年06月 - 2022年06月

[専門英語] 講座の講師　　　　　　　　　　　　　　　
School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
2022年01月 - 2022年01月

[Basic Clinical Medicine-I]講座の講師陣　　　　　　　　　　　　　　　
Hokkaido University, Faculty of Medicine and Graduate School of Medicine
2020年 - 2022年

[専門英語] 講座の講師　　　　　　　　　　　　　　　
School of Pharmaceutical Sciences, Fukuoka, Japan.
2021年07月 - 2021年07月

[生物薬学系英語講義-I]講座の講師　　　　　　　　　　　　　　　
School of Pharmaceutical Sciences, Fukuoka, Japan
2020年07月 - 2020年07月

Lecturer in the course Medical English for Beginners　　　　　　　　　　　　　　　
Faculty of Communication, Hokkaido University 2018-2019
2018年04月 - 2019年07月

Lecture in the couse ¨Pharmaceutical English II¨　　　　　　　　　　　　　　　
Faculty of Pharmacology Hokkaido University 2016-2018
2016年06月 - 2018年07月

Lecturer in the course "Medical English" for undergraduate medical students　　　　　　　　　　　　　　　
Faculty of Medicine Hokkaido University 2013-2018
2013年 - 2018年

Basic Clinical Medicine-I 講座の講師　　　　　　　　　　　　　　　
北海道大学
2009年 - 2016年

Invited teacher in the course “Communicating your research”　　　　　　　　　　　　　　　
Hokkaido University, Faculty of Science
2014年 - 2015年

Update Course in Rheumatology Junio 1999　　　　　　　　　　　　　　　
College of Physicians of Segovia, Spain
1999年06月 - 1999年07月

Preparatory course for Residents (MIR)　　　　　　　　　　　　　　　
Hospital Ramón y Cajal. Madrid, Spain
1993年 - 1994年

Consultant Rheumatologist at the Hospital General, Segovia, Spain　　　　　　　　　　　　　　　
Olga Amengual, 1998年06月 - 2002年05月, ［データベース］

Consultant iRheumatologist , Valdelaguila, Clinic Segovia, Spain　　　　　　　　　　　　　　　
Olga Amengual, 1997年07月 - 2002年05月, ［データベース］

Resident in Rheumatology at the Hospital Ramon y Cajal, Madrid Spain　　　　　　　　　　　　　　　
Olga Amengual, 1991年01月 - 1994年12月, ［データベース］

General Practitionner ( part time) at Primary Care Unit Segovia, Spain　　　　　　　　　　　　　　　
Olga Amengual, 1989年10月 - 1990年12月, ［その他］

日本人およびスペイン人の関節リウマチ患者における魚の摂取が標的治療薬の臨床効果に及ぼす影響について　　　　　　　　　　　　　　　
科学研究費助成事業 基盤研究(C)
2020年04月 - 2023年03月
Amengual Olga, 渥美 達也
During the first year, we researched food frequency questionnaires and, after consultation with nutritionists, the brief type self-administered diet history questionnaire (BDHQ) was selected and purchased. Japanese BDHQ was officially translated into Spanish. Another dietary questionnaire focusing on fish consumption was prepared and adapted to Spanish and Japanese population. We drafted the retrospective study protocol, patient's informed consent and data collection sheet in Japanese and Spanish. The documents were submitted to the Institutional Review Board of the two participating hospitals in Japan and Spain. By reviewing the medical records, patients with rheumatoid arthritis who were being treated with targeted therapies were identified.
日本学術振興会, 基盤研究(C), 北海道大学, 研究代表者, 20K11597

English learning for science, Agriculture and Engineering ( ELSAE) at Hokkaido University　　　　　　　　　　　　　　　
By the President ‘s Office ( Hokkaido University)
2015年04月 - 2016年03月
アメングアル オルガ
Grant for Research on development of educational programs, 研究代表者, 競争的資金

医学部及び医学研究科におけるグローバル化促進のための英語教育プログラム
科学研究費助成事業
2013年04月 - 2016年03月
Amengual Olga
医学教育英語コミュニケーション能力の重要性は増大している。前向き研究の目的は医学生に対する医学英語教育(medical English courses: MEC)の効果を検討した。医学部大学院博 が参加した。前後でvisual analogue scale(VAS)を用いて検討した（対象群）。MECを非受講のグループにも対象群と同期間のフォローアップ前後でVASを用い検討した（対照群）。対象群においては院生、学部生の双方で著明なVASの増大が認められ、英語コミュニケーションの自信(self-confidence)の獲得について、大きな効果があることが判明した。
日本学術振興会, 基盤研究(C), 北海道大学, 25350221

抗リン脂質抗体症候群にみられる血栓症の臓器特異性に関する研究　　　　　　　　　　　　　　　
JSPS-MEXT
2009年04月 - 2012年03月
アメングアル オルガ
Post-doctoral RPD-Fellowship from the Japan Society for the promotion of the Science (JSPS) and Ministry of Education, Science, Culture, Sports and Technology, 研究代表者, 競争的資金

Asymmetric distribution of cell membrane phospholipids: correlation with the pathogenesis of antiphospholipid syndrome　　　　　　　　　　　　　　　
JSPS
2003年09月 - 2005年09月
アメングアル オルガ
Post-doctoral Fellowship for foreign Scientist from the Japan Society for the promotion of the Science, 研究代表者, 競争的資金

Pre-doctoral Fellowship at St Thomas´ Hospital, London, UK　　　　　　　　　　　　　　　
FIS, Spain
1995年01月 - 1996年12月
アメングアル オルガ
Fondo de Investigaciones Sanitarias de la Seguridad Social, 研究代表者, 競争的資金