2020年12月, 日本免疫学会, 日本免疫学会研究奨励賞　　　　　　　　　　　　　　　

2020年06月, 公益財団法人 日本リウマチ財団, 塩川美奈子・膠原病研究奨励賞　　　　　　　　　　　　　　　

2020年03月, 北海道大学大学院医学研究院, 第39回高桑榮松奨学基金奨励賞　　　　　　　　　　　　　　　

2019年04月, 日本リウマチ学会, 奨励賞　　　　　　　　　　　　　　　
河野 通仁

2019年04月, 日本リウマチ学会, JCR 2019 Excellent Abstract Award　　　　　　　　　　　　　　　
河野 通仁

2018年12月, 平成30年度北海道大学医学部同窓会フラテ研究奨励賞　　　　　　　　　　　　　　　
河野 通仁

The increase of monocyte/high-density lipoprotein cholesterol ratio precedes recurrent thrombosis in patients with antiphospholipid syndrome.
Haruka Moriya, Ryo Hisada, Yuichiro Fujieda, Michihito Kono, Olga Amengual, Masaru Kato, Kazufumi Okada, Yoichi Ito, Tatsuya Atsumi
Rheumatology (Oxford, England), 2025年12月06日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is an emerging biomarker associated with inflammation and oxidative stress, being linked to cardiovascular events in patients with chronic kidney disease or those with diabetes. Given that monocyte activation plays a central role in the pathogenesis of thrombosis in antiphospholipid syndrome (APS), and that HDL-cholesterol suppresses monocyte activation, we aimed to investigate whether MHR could serve as a predictor for recurrent thrombotic events in APS patients. METHODS: This retrospective longitudinal study included 107 patients diagnosed with APS at Hokkaido University Hospital. The MHR at the time of APS diagnosis was calculated and compared between patients with and without subsequent thrombotic recurrence. Among patients who experienced recurrence, MHR values were compared between two time intervals prior to the event: 0-6 months and 6-36 months. RESULTS: The median [IQR] age at diagnosis was 46 [31-56] years, with a median follow-up duration of 14.4 [11.6-17.8] years. Thrombotic events recurred in 31 patients, including 22 arterial and 9 venous events. The MHR at diagnosis did not significantly differ between patients with and without recurrence (5.0 [3.4-8.0] vs 5.3 [3.5-8.6], p = 0.57). However, among patients with recurrent thrombosis, average MHR values during the 0-6 months preceding the event were significantly higher than those measured 6-36 months prior (6.1 [4.3-8.3] vs 5.1 [3.8-8.6], p = 0.04). CONCLUSION: Our findings suggest that MHR increases in the 6 months preceding recurrent thrombotic events in APS patients, indicating that it may serve as a dynamic, time-sensitive biomarker for predicting thrombotic recurrence in thrombotic APS.

Predictive Factors for Renal Outcome During Remission Induction Treatment Period in Lupus Nephritis.
Kazuro Kamada, Michihito Kono, Shuhei Takeyama, Ryo Hisada, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Tatsuya Atsumi
International journal of rheumatic diseases, 28, 11, e70470, 2025年11月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Patients with refractory lupus nephritis (LN) may benefit from the addition of anti-lupus drugs to standard remission induction therapy; however, which patients require additional treatment remains unclear. This study aimed to identify the predictive factors for renal outcomes during standard remission induction treatment for LN. METHODS: This retrospective observational study included 85 LN patients with standard remission induction therapy between 2006 and 2020. The baseline was the day of the initiation of remission induction therapy. Clinical and laboratory data were collected at 0, 2, 4, 8, 12 and 52 weeks after baseline. Complete renal remission (CRR) was defined as proteinuria < 0.5 g/gCr plus estimated glomerular filtration rate no worse than 10% below preflare value or ≥ 90 mL/min/1.73 m2 at 52 weeks. RESULTS: Among 85 patients, 48 (56.5%) achieved CRR at 52 weeks. Baseline serum creatinine (Cr) and proteinuria levels were not significantly different between the CRR and non-CRR groups. In the CRR group, the rate of decrease (%) in serum Cr at each period from baseline was significantly higher, while proteinuria at 12 weeks was significantly lower. Multivariate logistic regression identified the rate of decrease in serum Cr from baseline to 12 weeks (odds ratio = 1.25 [CI 1.03-1.55], p = 0.03) and proteinuria at 12 weeks (odds ratio = 0.71 [CI 0.49-0.95], p = 0.05) as independent predictive factors for CRR. Receiver operating characteristic curve analysis suggested proteinuria ≤ 0.8 g/gCr at 12 weeks as the best cutoff to predict CRR. CONCLUSIONS: The serum Cr decrease and proteinuria ≤ 0.8 g/gCr at 12 weeks were predictors of CRR.

Factors related to seroconversion of anti-cyclic citrullinated peptide antibody after the onset of rheumatoid arthritis: a case-control study and systematic review.
Yui Kosumi, Ryoko Asano, Aki Sugano, Masaru Yoshimura, Ryo Hisada, Michihito Kono, Yuichiro Fujieda, Tatsuya Atsumi, Masaru Kato
Immunological medicine, 1, 12, 2025年10月11日, ［国際誌］
英語, 研究論文（学術雑誌）, Anti-cyclic citrullinated peptide (CCP) antibodies typically present before rheumatoid arthritis (RA) but appear (seroconvert) after disease onset in some patients. This study analyzed factors related to anti-CCP seroconversion. Fifty-six consecutive patients with anti-CCP negative RA were enrolled. The first determination of anti-CCP status was defined as the baseline. Anti-CCP was then reassessed with an interval of 77 (±41) months. Demographics and baseline characteristics were compared between patients with and without anti-CCP seroconversion. Moreover, relevant studies were systematically reviewed. Six of the 56 patients experienced anti-CCP seroconversion (<4.5-12.4 [8.5-65.7] U/mL). These patients were more likely to have interstitial lung disease and HLA-DRB1 shared epitope (SE) alleles and to use biological disease-modifying antirheumatic drugs (bDMARDs). From the systematic review and meta-analysis, bDMARDs, bone erosions, HLA-DRB1 SE and rheumatoid factor positivity were identified as factors related to anti-CCP seroconversion. By selectively screening for anti-citrullinated protein antibody responses, an expansion of the repertoire was observed after the onset of RA. The seroconversion of anti-CCP after the onset of RA is associated with the typical features of RA and may therefore represent an overlooked seropositive disease.

Reasons for Breastfeeding Avoidance: A Multicenter Insight in Mothers With Systemic Lupus Erythematosus.
Massimo Radin, Silvia G Foddai, Karen Schreiber, Irene Cecchi, Flavio Signorelli, Guilherme de Jesús, Kuniyuki Aso, Michihito Kono, Maria Letizia Urban, Beatrice Bacco, Silvia Gallo Cassarino, Luca Lo Sardo, Marta Arbrile, 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
Journal of human lactation : official journal of International Lactation Consultant Association, 41, 3, 392, 400, 2025年08月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Limited research exists on breastfeeding among women with systemic lupus erythematosus, despite known benefits of human milk. RESEARCH AIM: To investigate reasons for breastfeeding avoidance among postpartum women with systemic lupus erythematosus. METHODS: This is a descriptive study, conducted in January 2023, combining retrospective pregnancy outcome data collection with a structured telephone questionnaire. RESULTS: Almost half of respondents (n = 22; 54.5%) experienced a disease flare within 24 months post-delivery. Reasons given by participants for breastfeeding avoidance included healthcare professional advice (n = 8; 36.4%), fear of medication harm (n = 5; 22.7%), and maternal/neonatal complications (n = 10; 45%). Most participants (n = 21; 95.5%) expressed a willingness to breastfeed if possible. CONCLUSION: Breastfeeding rates and breastfeeding specific care could be enhanced for patients with systemic lupus erythematosus through patient networks and appropriate practitioner education.

ADAM9 Promotes Glycolysis in Th17 Cells and Autoimmunity Through Activation of IGF-1 Signaling.
Kohei Karino, Masataka Umeda, Theodoros Vichos, Wenliang Pan, Michihito Kono, Maria G Tsokos, George C Tsokos
Arthritis & rheumatology (Hoboken, N.J.), 2025年07月21日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Interleukin-17-producing CD4+ Th17 cells contribute to the pathogenesis of autoimmune diseases, including crescentic glomerulonephritis. Although ADAM9 has been reported to contribute to organ inflammation, the mechanism remains poorly understood. The goal of the current study was to investigate how ADAM9 alters T cell metabolism to promote the generation of Th17 cell differentiation. METHODS: We induced antiglomerular basement membrane (anti-GBM) glomerulonephritis in Adam9+/+ and Adam9-/- mice using sheep anti-GBM IgG and compared disease severity. Glycolysis in Th17 cells was measured using a Seahorse XFp Extracellular Flux Analyzer (Agilent Technologies, Inc), and metabolomic analysis was conducted on Th17 cells from both Adam9+/+ and Adam9-/- mice. We measured the GLUT1 expression in Th17 cells from Adam9+/+ and Adam9-/- mice and insulin-like growth factor 1 (IGF-1)-treated Th17 cells. Finally, we assessed the protease activity of ADAM9 on IGF-binding protein 4 (IGFBP4). RESULTS: Mice deficient in ADAM9 had limited numbers of kidney-infiltrating CD4+ T cells and suffered reduced kidney damage and inflammation following the injection of sheep anti-GBM IgG. ADAM9 deficiency led to decreased GLUT1 expression and glycolysis in Th17 cells. Mechanistically, we found that ADAM9 cleaved IGFBP4 and enabled the release of IGF-1, which enhanced the expression of GLUT1 and promoted glycolysis. CONCLUSION: By cleaving IGFBP4, ADAM9 releases IGF-1, which in turn upregulates GLUT1 expression and promotes glycolysis in Th17 cells. These findings suggest that targeting ADAM9 or blocking IGF-1 should provide a therapeutic strategy for autoimmune diseases.

Potential Biomarkers in Systemic Lupus Erythematosus.
Yujie Song, Michihito Kono
JMA journal, 8, 3, 689, 698, 2025年07月15日, ［国内誌］
英語, 研究論文（学術雑誌）, Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by heterogeneous clinical manifestations and diverse autoantibody production. Despite advances in treatment, many patients experience disease flares throughout their lives, and current biomarkers like anti-double-stranded DNA antibodies and serum complement levels have limitations in accurately reflecting disease activity. This review examines emerging and established biomarkers for SLE diagnosis, disease activity monitoring, and treatment response prediction. We discuss immune cell subsets as potential biomarkers, focusing on plasmacytoid dendritic cells, T cell and B cell subsets, especially focused on T cell subsets. The review highlights how imbalances in these cellular populations correlate with disease activity and specific organ involvement. Furthermore, we discuss cytokines, chemokines, autoantibodies, and complement as biomarkers in SLE. The identification and validation of reliable biomarkers in SLE will ultimately improve clinical decision-making regarding treatment selection, glucocorticoid tapering, and prediction of disease remission, leading to more personalized and effective management strategies.

Sulfasalazine as a Prophylactic for Pneumocystis Pneumonia in Patients With Rheumatoid Arthritis: A Cohort Study.
Masaru Yoshimura, Nobuya Abe, Michihito Kono, Koji Oba, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Tatsuya Atsumi
International journal of rheumatic diseases, 28, 6, e70325, 2025年06月, ［国際誌］
英語, 研究論文（学術雑誌）, AIM: We investigated the potential of sulfasalazine (SSZ), one of the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA). METHODS: In this longitudinal cohort study, we enrolled patients with RA who started receiving new RA treatment. A treatment episode was defined as a period of 1 year from the start or increase of DMARDs dose, or starting prednisolone > 10 mg/day, and the incidence of PCP in this period was assessed. All treatment episodes were classified into two groups based on the presence of SSZ at baseline. The PCP incidence rate in the two groups was evaluated using a negative binomial regression model. RESULTS: A total of 848 treatment episodes were recorded in 594 RA patients: 181 and 667 in the SSZ and control groups, respectively. During the 850.6 person-years of observation, 21 patients developed PCP, and three died of PCP. Multivariable adjusted analysis using Firth's method showed that the 1-year incidence of PCP was significantly reduced with SSZ treatment (p = 0.003, rate ratio = 0.05; 95% CI 0.00-0.34). Furthermore, the log-rank test in the propensity score-matched population confirmed this result. Regarding safety, 45 adverse drug reactions related to SSZ occurred (4.34/100 person-years; 95% CI 3.26-5.78). Only one serious adverse reaction (drug-induced hypersensitivity syndrome) was observed, which resolved after discontinuation of SSZ. CONCLUSION: We demonstrated the preventive efficacy of SSZ on PCP. The pleiotropic effect of this traditional DMARD may impact RA treatment, providing another option for PCP prophylaxis.

Impact of glucocorticoid tapering speed on renal outcomes in proliferative lupus nephritis: a multicentre retrospective study.
Koichiro Ohmura, Hayato Shimizu, Yoshiya Tanaka, Keiju Hiromura, Hiroki Hayashi, Kazuro Kamada, Kentaro Minowa, Yutaka Kawahito, Akiho Iwashita, Shinya Kaname, Shinsuke Yasuda, Kazuoto Hiramoto, Shoichi Maruyama, Nobuyuki Yajima, Yasunori Iwata, Isao Matsumoto, Takahisa Gono, Hiroko Sato, Satoshi Kubo, Singo Nakayamada, Hidekazu Ikeuchi, Yukio Yuzawa, Michihito Kono, Naoto Tamura, Takahiro Seno, Takashi Kida, Aki Sakashita, Akira Onishi, Akio Morinobu, Takahisa Kawakami, Tadashi Hosoya, Taiki Yamaguchi, Yuko Kaneko, Hironari Hanaoka, Sawako Kato, Kayaho Maeda, Shiori Nakagawa, Yuya Kondo, Masataka Kuwana, Tomonori Ishii, Shuji Sumitomo, Chisato Miyakoshi, Tatsuya Atsumi
Rheumatology (Oxford, England), 2025年05月13日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Recent guidelines and recommendations for lupus nephritis (LN) suggest rapid glucocorticoid (GC) reduction; however, robust supporting evidence remains limited. This study aimed to evaluate the impact of rapid GC reduction on renal outcomes in patients with proliferative LN. METHODS: We conducted a multicentre retrospective chart review of patients with GC-naïve, biopsy-proven proliferative LN with available urinary protein-to-creatinine ratio (UPCR) data before and 52 weeks after GC treatment. Patients who reduced their prednisolone-equivalent dose to ≤ 7.5 mg/day within 6 months (rapid GC reducers) were compared with those who did not (conventional GC reducers) regarding partial renal response (PRR) at 12 months. Modified Poisson regression analysis was used to adjust for confounding factors. RESULTS: A total of 344 patients from 17 centres were included: 50 rapid GC reducers and 294 conventional GC reducers. PRR at 12 months was achieved by 43/50 (86%) in the rapid GC group and 248/294 (84.4%) in the conventional group. After adjusting for age, initial UPCR, initial estimated glomerular filtration rate, the presence of a concomitant membranous lesion in the glomerulus, initial GC dose, use of methylprednisolone pulse therapy, strong immunosuppressants (mycophenolate mofetil, cyclophosphamide, or rituximab), and hydroxychloroquine, no significant difference was observed in PRR at 12 months (adjusted risk ratio: 0.92, p= 0.758). Relapse rates and serious adverse events over 2 years of follow-up were also comparable between the groups. CONCLUSION: Rapid GC reduction to ≤ 7.5 mg/day within 6 months did not compromise renal outcomes or increase relapse in proliferative LN.

Subacute Finger Gangrene with Severe Raynaud's Phenomenon.
Kazuro Kamada, Michihito Kono, Tatsuya Atsumi
Internal medicine (Tokyo, Japan), 2025年03月15日, ［国内誌］
英語, 研究論文（学術雑誌）

本邦における血栓性微小血管症を伴う全身性エリテマトーデス患者の特性と臨床所見 ケースシリーズ研究　　　　　　　　　　　　　　　
奥 健志, 渥美 達也, 河野 通仁, 石井 智徳, 町山 智章, 松下 雅和, 河本 敏雄, 河野 正憲, 下野 明彦, 藤尾 圭志
日本リウマチ学会総会・学術集会プログラム・抄録集, 69回, 710, 710, (一社)日本リウマチ学会, 2025年03月
日本語

若年全身性エリテマトーデス患者における睡眠健康状態と精神神経症状との関連性 PLEASURE-Jコホートを用いた検討　　　　　　　　　　　　　　　
吉村 大, 藤枝 雄一郎, 久田 諒, 河野 通仁, 磯島 咲子, 一瀬 邦弘, 岩田 恭宜, 奥 健志, 金子 佳代子, 佐田 憲映, 田中 良哉, 藤尾 圭志, 松下 雅和, 宮前 多佳子, 村島 温子, 中島 亜矢子, 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, 69回, 772, 772, (一社)日本リウマチ学会, 2025年03月
日本語

Recent advances in immunometabolism in rheumatic diseases.
Ryo Hisada, Michihito Kono
Current opinion in rheumatology, 37, 2, 142, 148, 2025年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE OF REVIEW: Aberrant autoreactive innate and adaptive immune responses cause systemic autoimmune diseases. Autoimmunity has been linked to abnormal metabolic states, and immunometabolism has emerged as a critical field in understanding the pathogenesis of rheumatic diseases. We aimed to explore the latest research on metabolic reprogramming in various immune cell types, including T cells, B cells, neutrophils, dendritic cells, monocytes, and macrophages, in the context of rheumatic diseases. RECENT FINDINGS: Each immune cell utilizes preferred metabolic pathways, and the cell activation dramatically modifies metabolic status. The inhibition of these pathways alters cell survival, differentiation, proliferation, and cytokine production - all of which contribute to rheumatic disease progression. SUMMARY: Targeting metabolic pathways or introducing anti-inflammatory metabolites, such as itaconate, could be novel therapeutic strategies for rheumatic diseases. Further research should focus on strategies for translating basic research findings to bedside applications.

Metabolites as regulators of autoimmune diseases.
Maria Tada, Michihito Kono
Frontiers in immunology, 16, 1637436, 1637436, 2025年, ［国際誌］
英語, 研究論文（学術雑誌）, Immune cell metabolism is essential for regulating immune responses, including activation, differentiation, and function. Through glycolysis and oxidative phosphorylation (OXPHOS), metabolism supplies energy and key intermediates for cell growth and proliferation. Importantly, some metabolites generated during these processes act as signaling molecules that influence immune activity. Autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) involve multiple immune cell types, and recent research in immunometabolism has revealed that disrupted metabolic pathways in these cells contribute to disease progression. Effector T cells, for instance, undergo metabolic reprogramming, particularly increased glycolysis, to meet the demands of proliferation and function during autoimmune responses. Targeting metabolic enzymes has shown therapeutic potential. In addition, metabolites themselves, termed immunometabolites, can directly modulate immune responses. These include both intracellularly generated and secreted molecules. Itaconate is a key immunometabolite and is derived from the TCA cycle by aconitate decarboxylase 1 (ACOD1) in activated macrophages. It inhibits the NLRP3 inflammasome and pro-inflammatory cytokines, such as IL-1β and IL-6. Beyond macrophages, itaconate alters metabolism and epigenetics in T cells by reducing 2-hydroxyglutarate and the S-adenosyl-L-methionine (SAM)/S-adenosyl-L-homocysteine (SAH) ratio, thereby suppressing Th17 differentiation and enhancing Foxp3 expression in Tregs. Itaconate ameliorates disease in experimental autoimmune encephalomyelitis, RA, SLE, and others. It also exhibits antimicrobial effects by blocking bacterial isocitrate lyase and viral replication. Despite increasing interest, reviews focusing specifically on immunometabolites remain limited. This review highlights emerging insights into metabolites involved in glycolysis, the TCA cycle, glutaminolysis, one-carbon metabolism, and lipid metabolism that influence autoimmune pathophysiology.

Muscle vasculitis in patients with polymyalgia rheumatica; three case series.
Haruka Moriya, Yuichiro Fujieda, Yuta Inoue, Kenichi Miyamoto, Mamiko Anada, Daiki Tanaka, Akihiko Kudo, Megumi Abe, Azusa Nagai, Ryo Hisada, Michihito Kono, Masaru Kato, Olga Amengual, Yoshihiro Matsuno, Ichiro Yabe, Tatsuya Atsumi
Modern rheumatology case reports, 2024年12月09日, ［国際誌］
英語, 研究論文（学術雑誌）, Polymyalgia rheumatica (PMR) is a common inflammatory disorder characterized by myalgia/stiffness in proximal hip and shoulder girdle, elevated C reactive protein (CRP) and erythrocyte sedimentation rate (ESR), but its pathogenesis is not fully elucidated. We report three cases of PMR who do not respond adequately to standard treatment. Those patients had typical symptoms of myalgia and muscle weakness, with elevated CRP in absence of creatine kinase elevation. Muscle specimen showed the findings of vasculitis in all cases, therefore muscular limited vasculitis (MLV) may be an underlying pathology in PMR in those refractory cases.

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.

Potential therapies targeting metabolic pathways in systemic lupus erythematosus.
Ryo Hisada, Michihito Kono
Clinical immunology (Orlando, Fla.), 263, 110224, 110224, 2024年06月, ［国際誌］
英語, 研究論文（学術雑誌）, The pathophysiology of systemic lupus erythematosus (SLE) is multifactorial and involves alterations in metabolic pathways, including glycolysis, lipid metabolism, amino acid metabolism, and mitochondrial dysfunction. Increased glycolysis in SLE T cells, which is associated with elevated glucose transporter 1 expression, suggests targeting glucose transporters and hexokinase as potential treatments. Abnormalities in lipid metabolism, particularly in lipid rafts and enzymes, present new therapeutic targets. This review discusses how changes in glutaminolysis and tryptophan metabolism affect T-cell function, suggesting new therapeutic interventions, as well as mitochondrial dysfunction in SLE, which increases reactive oxygen species. The review also emphasizes that modulating metabolic pathways in immune cells is a promising approach for SLE treatment, and can facilitate personalized therapies based on individual metabolic profiles of patients with SLE. The review provides novel insights into strategies for managing SLE.

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.

SARS-CoV-2ワクチン接種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産生を亢進させうる　　　　　　　　　　　　　　　
安田 充孝, 藤枝 雄一郎, 守谷 悠, 久田 諒, 河野 通仁, 加藤 将, Amengual Olga, 安本 篤史, 森下 英理子, 浦野 哲盟, 渥美 達也
日本血栓止血学会誌, 35, 2, 304, 304, (一社)日本血栓止血学会, 2024年05月
日本語

Decrease in Mycophenolic Acid Plasma Level by Sacubitril/Valsartan in a Lupus Nephritis Patient: A Case Report.
Shunsuke Nashimoto, Masashi Miyamae, Issei Higuchi, Michihito Kono, Maria Tada, Tatsuya Atsumi, Mitsuru Sugawara, Yoh Takekuma
Case reports in nephrology and dialysis, 14, 1, 30, 35, 2024年, ［国際誌］
英語, INTRODUCTION: Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case report, the area under the blood concentration time curve (AUC) of MPA was significantly decreased by the concomitant use of sacubitril/valsartan. CASE PRESENTATION: The patient was a man in his 40s with a diagnosis of lupus nephritis class IVa/c+V. MMF dose was 1.5 g/day at admission, and AUC of MPA on day 14 was 25.1 μg⋅h/mL. Owing to poor blood pressure control, sacubitril/valsartan was initiated at 97/103 mg/day on day 29. On day 37, AUC of MPA was significantly decreased to 8.7 μg⋅h/mL, suggesting drug interaction with the newly initiated sacubitril/valsartan. Sacubitril/valsartan was decreased to 49/51 mg/day, and AUC of MPA on day 67 was 37.6 μg⋅h/mL, achieving the target range. The final MMF dose was set at 1.75 g/day. A possible mechanism of drug interaction between sacubitril/valsartan and MPA involves an organic anion transporting polypeptide (OATP). The inhibition of OATPs by sacubitril may have interrupted the enterohepatic circulation of MPA, resulting in a lower plasma concentration. CONCLUSION: Since lupus nephritis is often associated with hypertension, the drug interaction observed in this report may also occur in other cases. However, it is impossible to conclude that the decrease in plasma MPA levels was due to the concomitant use of sacubitril/valsartan, and more cases and basic findings are needed.

Granzyme K- and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease.
Risako Koga, Takashi Maehara, Ryuichi Aoyagi, Ryusuke Munemura, Yuka Murakami, Atsushi Doi, Michihito Kono, Hidetaka Yamamoto, Hiroaki Niiro, Tamotsu Kiyoshima, Mika Tanabe, Toshiaki Nakano, Yuta Matsukuma, Mitsuhiro Kawano, John H Stone, Shiv Pillai, Seiji Nakamura, Shintaro Kawano
The Journal of allergy and clinical immunology, 153, 4, 1095, 1112, 2023年12月11日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: IgG4-related disease (IgG4-RD), an example of a type I immune disease, is an immune-mediated fibrotic disorder characterized by dysregulated resolution of severe inflammation and wound healing. However, truly dominant or pathognomonic autoantibodies related to IgG4-RD are not identified. OBJECTIVE: We performed single-cell RNA sequencing (scRNA-seq) and T-cell receptor (TCR) and B-cell receptor (BCR) sequencing to obtain a comprehensive, unbiased view of tissue-infiltrating T- and B-cells. METHODS: We performed unbiased scRNA-seq analysis for the transcriptome and TCR-seq and BCR-seq on sorted CD3+ T- or CD19+ B-cells from affected tissues of patients with IgG4-RD. We also conducted quantitative analyses of CD3+ T and CD19+ B subsets in 68 IgG4-RD and 30 Sjögren's syndrome (SjS) patients. RESULTS: Almost all clonally expanded T cells in these lesions were either Granzyme K (GZMK)-expressing CD4+ cytotoxic T cells (CTLs) or GZMK+CD8+ T cells. These GZMK-expressing CTLs also expressed amphiregulin and TGFβ but did not express immune-checkpoints, and the tissue-infiltrating CD8+ T cells were phenotypically heterogeneous. MKI67+ B cells and IgD-CD27-CD11c-CXCR5- double-negative 3 B cells were clonally expanded and infiltrated affected tissue lesions. GZMK+CD4+ CTLs co-localized with MKI67+ B cells in the extrafollicular area from affected tissue sites. CONCLUSION: The abovementioned cells likely participate in T-B collaborative events, suggesting possible avenues for targeted therapies. Our findings were validated using orthogonal approaches, including multicolor immunofluorescence and the use of comparator disease groups, to support the central role of cytotoxic CD4+ and CD8+ T cells expressing GZMK, amphiregulin, and TGFβ in the pathogenesis of inflammatory fibrotic disorders.

Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue With Spontaneous Shrinkage in a Patient With Sjögren Syndrome.
Kodai Sakiyama, Michihito Kono, Ai Shimizu, Tatsuya Atsumi
The Journal of rheumatology, 2023年10月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Patients with Sjögren syndrome (SS) have a higher risk of developing malignant lymphoma.1A 68-year-old woman presented with a 2-month history of swollen parotid glands. The patient had psoriatic arthritis and had been treated with secukinumab for 3 months.

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), 63, 7, 1868, 1873, 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.

Angioedema: hereditary or C1-inhibitor deficiency associated with systemic lupus erythematosus?
Michihiro Kono, Michihito Kono, T Atsumi
Scandinavian journal of rheumatology, 52, 6, 1, 2, 2023年07月13日, ［国際誌］
英語, 研究論文（学術雑誌）

Reply.
Kohei Karino, Michihito Kono, Tatsuya Atsumi, Masatoshi Kanda
Arthritis & rheumatology (Hoboken, N.J.), 75, 7, 1294, 1296, 2023年07月, ［国際誌］
英語

Dynamics of corticocortical brain functional connectivity relevant to therapeutic response to biologics in inflammatory arthritis.
Kodai Sakiyama, Nobuya Abe, Yuichiro Fujieda, Khin K Tha, Hisashi Narita, Kohei Karino, Masatoshi Kanda, Michihito Kono, Masaru Kato, Tatsuya Atsumi
Cerebral cortex (New York, N.Y. : 1991), 33, 13, 8342, 8351, 2023年04月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Aberrant functional connectivity (FC) of the brain regions, evaluated by functional magnetic resonance imaging (fMRI), affects clinical courses in inflammatory arthritis (IA). The static analysis methods would be simplistic to estimate the whole picture of resting-state brain function because blood oxygen level-dependent (BOLD) signals fluctuate over time. The effects of FC dynamics on clinical course are unknown in IA. Therefore, we aimed to evaluate dynamic FC for therapeutic responsiveness to biologics in IA patients. We analyzed resting-state fMRI data of 64 IA patients in 2 cohorts. Dynamic FC was derived as a correlation coefficient of the windowed BOLD signal time series. We determined representative whole-brain dynamic FC patterns by k-means++ cluster analysis, leading to 4 distinct clusters. In the first cohort, occurrence probability of the distinct cluster was associated with favorable therapeutic response in disease activity and patients' global assessment, which was validated by the second cohort. The whole-brain FC of the distinct cluster indicated significantly increased corticocortical connectivity, and probabilistically decreased after therapy in treatment-effective patients compared with -ineffective patients. Taken together, frequent emergence of corticocortical connections was associated with clinical outcomes in IA. The coherence of corticocortical interactions might affect pain modulation, possibly relevant to therapeutic satisfaction.

New insights into the metabolism of Th17 cells.
Michihito Kono
Immunological medicine, 46, 1, 15, 24, 2023年03月, ［国際誌］
英語, 研究論文（学術雑誌）, T helper 17 (Th17) cells are IL-17-producing CD4 T cells that play a crucial role in autoimmune diseases. IL-17 is a key cytokine for host protection against mucosal and skin infection but is also one of the major pathogenic cytokines. IL-1 and IL-23 are requisite for stimulating pathogenic Th17 cell differentiation and proliferation. Therapeutics targeting the IL-17/IL-23 pathway are widely used clinically for the treatment of autoimmune diseases. Besides IL-17, pathogenic Th17 cells produce granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, interferon γ, IL-21 and IL-22. However, Th17-targeted therapy has not yet been established. T cell metabolism orchestrates T cell survival, cell differentiation, epigenetic change and function and each T cell subset favors a particular metabolic pathway. Recent studies have provided novel insights into the role of T cell metabolism in the pathogenesis of autoimmune diseases. The current review focuses on the role of Th17 cell metabolism in autoimmune diseases, particularly glycolysis, amino acid metabolism, lipid metabolism, as well as the regulators of these processes, including mTORC1. Therapeutics targeting T cell metabolism in autoimmune diseases could serve as a possible treatment option for patients who are refractory to or unresponsive to conventional therapy.

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, 984, 984, Springer Science and Business Media LLC, 2023年02月27日, ［国際誌］
英語, 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.

Beneficial effects of nintedanib on cardiomyopathy in patients with systemic sclerosis: a pilot study.
Keita Ninagawa, Masaru Kato, Satonori Tsuneta, Suguru Ishizaka, Hideyuki Ujiie, Ryo Hisada, Michihito Kono, Yuichiro Fujieda, Yoichi M Ito, Tatsuya Atsumi
Rheumatology (Oxford, England), 62, 7, 2550, 2555, 2022年12月02日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Nintedanib is an inhibitor of tyrosine kinases that has been shown to slow the progression of interstitial lung disease (ILD), including ILD associated with systemic sclerosis (SSc). The aim of this study was to explore the effect of nintedanib on cardiomyopathy associated with SSc. METHODS: Twenty consecutively hospitalized patients with SSc-ILD were enrolled and prospectively followed. The rate of change at six months in cardiac magnetic resonance (CMR) parametric mapping, including myocardial extracellular volume, was primarily evaluated. Other endpoints included changes in CMR functional parameters, echocardiographic parameters, modified Rodnan skin score, serum biomarkers, and pulmonary function test. RESULTS: Nintedanib was administered in 10 patients, whereas the other 10 were treated without nintedanib or watched, according to ILD severity and progression. Baseline values of CMR parametric mapping were not different between the two groups. The rate of change at six months in myocardial extracellular volume was largely different, almost divergent between the nintedanib group and the control group (-1.62% vs. +2.00%, p= 0.0001). Among other endpoints, the change in right ventricular ejection fraction was significantly different between the two groups (p= 0.02), with a preferential change in the nintedanib group. CONCLUSION: Our data indicate beneficial signals of nintedanib on cardiomyopathy associated with SSc. The anti-fibrotic effect of nintedanib might not be limited to the lung.

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, ［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, ［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.

Predicting the response to pulmonary vasodilator therapy in systemic sclerosis with pulmonary hypertension by using quantitative chest CT.
Keita Ninagawa, Masaru Kato, Yasuka Kikuchi, Hiroyuki Sugimori, Michihito Kono, Yuichiro Fujieda, Ichizo Tsujino, Tatsuya Atsumi
Modern rheumatology, 33, 4, 758, 767, 2022年09月02日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Systemic sclerosis (SSc) is associated with pulmonary vascular disease (PVD) and interstitial lung disease (ILD), making it difficult to differentiate pulmonary arterial hypertension and pulmonary hypertension (PH) due to lung diseases and/or hypoxia and to decide treatments. We aimed to predict the response to pulmonary vasodilators in patients with SSc and PH. METHODS: 84 SSc patients were included with 47 having PH. Chest CT was evaluated using a software to calculate abnormal lung volume (ALV). To define the response to vasodilators, Δ mean pulmonary artery pressure (mPAP)/basal mPAP was used (cut-off value: 10%). The predictive value was evaluated by using receiver operating characteristic curve. RESULTS: The mean (±SD) value of ALV was 26.8 (±32.2) %. A weak correlation was observed between ALV and forced vital capacity (FVC) (R = -0.46). The predictive value of ALV (area under curve; AUC = 0.74) was superior to that of FVC (AUC = 0.62) for the response to vasodilators. No hemodynamic parameters differed between patients with high and low ALV, whereas survival was worse in high ALV. CONCLUSION: Quantitative chest CT well predicted the response to vasodilators in patients with SSc and PH. Our results suggest its utility in differentiating the dominance of PVD or ILD.

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, ［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.

The deacetylase SIRT2 contributes to autoimmune disease pathogenesis by modulating IL-17A and IL-2 transcription.
Ryo Hisada, Nobuya Yoshida, Masataka Umeda, Catalina Burbano, Rhea Bhargava, Marc Scherlinger, Michihito Kono, Vasileios C Kyttaris, Suzanne Krishfield, George C Tsokos
Cellular & molecular immunology, 19, 6, 738, 750, 2022年05月06日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Aberrant IL-17A expression together with reduced IL-2 production by effector CD4+ T cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report that Sirtuin 2 (SIRT2), a member of the family of NAD+-dependent histone deacetylases, suppresses IL-2 production by CD4+ T cells while promoting their differentiation into Th17 cells. Mechanistically, we show that SIRT2 is responsible for the deacetylation of p70S6K, activation of the mTORC1/HIF-1α/RORγt pathway and induction of Th17-cell differentiation. Additionally, SIRT2 was shown to be responsible for the deacetylation of c-Jun and histones at the Il-2 gene, resulting in decreased IL-2 production. We found that the transcription factor inducible cAMP early repressor (ICER), which is overexpressed in T cells from people with SLE and lupus-prone mice, bound directly to the Sirt2 promoter and promoted its transcription. AK-7, a SIRT2 inhibitor, limited the ability of adoptively transferred antigen-specific CD4+ T cells to cause autoimmune encephalomyelitis in mice and limited disease in lupus-prone MRL/lpr mice. Finally, CD4+ T cells from SLE patients exhibited increased expression of SIRT2, and pharmacological inhibition of SIRT2 in primary CD4+ T cells from patients with SLE attenuated the ability of these cells to differentiate into Th17 cells and promoted the generation of IL-2-producing T cells. Collectively, these results suggest that SIRT2-mediated deacetylation is essential in the aberrant expression of IL-17A and IL-2 and that SIRT2 may be a promising molecular target for new SLE therapies.

Diagnostic Value of Vessel Wall Imaging to Determine the Timing of Extracranial-Intracranial Bypass for Moyamoya Syndrome Associated with Active Sjögren's Syndrome: A Case Report.
Takafumi Shindo, Masaki Ito, Taku Sugiyama, Tomohiro Okuyama, Michihito Kono, Tatsuya Atsumi, Miki Fujimura
Journal of neurological surgery. Part A, Central European neurosurgery, 2022年04月22日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Sjögren's syndrome is a chronic autoimmune disorder that predominantly affects exocrine organs. It is characterized by an organ-specific infiltration of lymphocytes. The involvement of the major cerebral arteries in Sjögren's syndrome has rarely been reported. A recent study reported a case of successful extracranial‒intracranial (EC‒IC) bypass without complications, even in the active inflammatory state, although the optimal timing of such a bypass remains unclear. CASE DESCRIPTION: We here report the case of a 43-year-old woman presenting with acute ischemic stroke due to progressive middle cerebral artery (MCA) occlusion and signs of primary Sjögren's syndrome. During intensive immunosuppressive therapy for active Sjögren's syndrome, the patient was monitored using contrast-enhanced magnetic resonance vessel wall imaging (MR-VWI). A couple of intravenous cyclophosphamide injections combined with a methylprednisolone pulse and antiplatelet therapy, resulted in clear resolution of vessel wall enhancement, which suggested remission of inflammatory vasculitis. Nevertheless, she still experienced a transient ischemic attack due to decreased regional cerebral blood flow by MCA occlusion, as demonstrated by the conventional time-of-flight MR angiography and single-photon emission computed tomography. Considering the increased risk of further stroke, the decision was made to perform EC-IC bypass as a treatment of hemodynamic impairment medically uncontrollable. Her postoperative course was uneventful without further repeated TIAs, and continued immunosuppressive therapy for Sjögren's syndrome provided effective management. CONCLUSIONS: Our findings emphasize the diagnostic value of contrast-enhanced MR-VWI in monitoring the effect of immunosuppressive therapy for the major cerebral artery vasculitis and in determining the timing of EC‒IC bypass as a 'rescue' treatment for Moyamoya syndrome associated with active Sjögren's syndrome.

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.

Glutaminase 2 Promotes Interleukin-2 Production in CD4+ T cells by Supporting Antioxidant Defense.
Ryo Hisada, Nobuya Yoshida, Seo Yeon K Orite, Masataka Umeda, Catalina Burbano, Marc Scherlinger, Michihito Kono, Suzanne Krishfield, George C Tsokos
Arthritis & rheumatology (Hoboken, N.J.), 74, 7, 1204, 1210, 2022年03月07日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Glutaminase (GLS) isoenzymes GLS1 and GLS2 catalyze the first step of glutaminolysis. GLS1 is requisite for Th17 differentiation and its inhibition suppresses autoimmune disease in animals but the function of GLS2 is not known. The aim of this study was to investigate the role of GLS2 in CD4+ T cell function and systemic lupus erythematosus (SLE) pathogenesis. METHODS: We measured reactive oxygen species (ROS) levels, lipid peroxidation, and mitochondrial mass/polarization by flow cytometry, IL-2 production by dual luciferase assay, and CpG-DNA methylation of the Il-2 gene by real-time PCR. The impact of the overexpression of wild type GLS1 and GLS2, or mutated GLS2 at the PDZ domain-binding motif in CD4+ T cells was examined. Furthermore, GLS2 expression in CD4+ T cells from lupus-prone mice and patients with SLE was analyzed by Western blotting. RESULTS: GLS2, but not GLS1, reduced ROS levels, lipid peroxidation and restored mitochondrial function in T cells. GLS2 promoted IL-2 production through the demethylation of the Il-2 promoter. Mutation of the PDZ domain-binding motif abated the ability of GLS2 to regulate IL-2 and ROS levels. In lupus-prone mice and patients with SLE, the expression of GLS2 was decreased in CD4+ T cells. Finally, GLS2 overexpression corrected ROS levels and restored IL-2 production by lupus CD4+ cells. CONCLUSION: Our findings suggest that GLS2 has a crucial role in IL-2 production by CD4+ T cells by supporting the antioxidant defense and offer a new approach to correct IL-2 production by T cell in SLE.

Glycogen synthase kinase 3β/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO.
Nobuya Abe, Michihito Kono, Michihiro Kono, Naoki Ohnishi, Tomoya Sato, Masato Tarumi, Masaru Yoshimura, Taiki Sato, Kohei Karino, Yuka Shimizu, Yuichiro Fujieda, Masaru Kato, Rie Hasebe, Kenji Oku, Masaaki Murakami, Tatsuya Atsumi
British journal of haematology, 196, 5, 1194, 1204, 2022年03月, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Multicentric Castleman disease-thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD-TAFRO)-is an emergent phenotype characterized by lymphoproliferation, fluid collection, hemocytopenia and multiple organopathy. Although studies have demonstrated an aberrant blood cytokine/chemokine profile referred to as "chemokine storm", the pathogenesis remains unclear. We aimed to identify pathogenic key molecules, potential diagnostic targets and therapeutic markers in MCD-TAFRO using serum cytokine/chemokine profiles. We performed the targeted cytokine/chemokine multiplex analysis in six cases of MCD-TAFRO with remission or non-remission status. We observed significant changes in serum concentrations of CCL2, CCL5, and Chitinase-3-like-1 in the MCD-TAFRO patients with active state compared to inactive state. Ingenuity pathway analysis revealed that glycogen synthase kinase 3 (GSK3) and CCR6, which is expressed in megakaryocytes, were detected as upstream positive regulators for activating MCD-TAFRO status. More GSK3β+ CCR6+ cells like megakaryocytes were detected in the bone marrow of patients with MCD-TAFRO than in those with systemic lupus erythematosus, MCD-not otherwise specified or autoimmune haemophagocytic lymphohistiocytosis. The cellularity of GSK3β+ CCR6+ cells was correlated with disease activity, including thrombocytopenia and anaemia. In conclusion, GSK3β and CCR6 of bone marrow cells were potentially involved in the pathogenesis of MCD-TAFRO and may act as diagnostic targets and therapeutic markers.

Anti-Ganglionic Nicotinic Acetylcholine Receptor Α3 Subunit Antibody as a Potential Biomarker Associated With Lupus Enteritis.
Kuniyuki Aso, Michihito Kono, Nobuya Abe, Yuichiro Fujieda, Masaru Kato, Tatsuya Atsumi
Modern rheumatology, 33, 1, 154, 159, 2022年02月02日, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: We aimed to identify the clinical significance of anti-ganglionic nicotinic acetylcholine receptor α3 subunit (gAChRα3) antibodies (Abs) in patients with systemic lupus erythematosus (SLE). METHODS: This retrospective study comprised adult patients with SLE who visited our hospital from 2006 through 2019. Anti-gAChRα3 Abs were measured in the sera of patients with SLE using a luciferase immunoprecipitation system assay. The clinical features of the patients with or without anti-gAChRα3 Abs were compared. We evaluated whether the Abs predict a specific manifestation and affect its development or relapse rate. RESULTS: Among 144 patients, anti-gAChRα3 Abs were detected in 29 patients. Lupus enteritis (LE) was more frequently seen in anti-gAChRα3 Ab-positive patients than negative patients. The levels of anti-gAChRα3 Abs were significantly higher in patients with LE than those with other lupus manifestations. Logistic regression analysis revealed the anti-gAChRα3 Abs were independent predictors for LE (odds ratio 6.2, 95% confidence interval 1.9-20.3, p = 0.002). Kaplan-Meier analysis showed the rate of LE development or relapse from the time of sera collection was higher in anti-gAChRα3 Ab-positive patients than in negative patients (p < 0.001). CONCLUSION: Anti-gAChRα3 Abs could be a predictive biomarker for the development or relapse of LE.

Cytokine and chemokine multiplex analysis-based exploration for potential treatment and prognostic prediction in large-vessel vasculitis: A preliminary observational study.
Nobuya Abe, Michihiro Kono, Michihito Kono, Takayuki Katsuyama, Kazumasa Ohmura, Taiki Sato, Kohei Karino, Yuichiro Fujieda, Masaru Kato, Rie Hasebe, Masaaki Murakami, Tatsuya Atsumi
Frontiers in immunology, 13, 1066916, 1066916, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Large-vessel vasculitis (LVV) is subclassified into two phenotypes; Takayasu arteritis and giant cell arteritis. Although the pathogenesis of LVV is not fully established, IL-6-IL-17 axis and IL-12-IFN-γ axis play critical roles in the disease development. We aimed to clarify the association between the disease state and cytokine/chemokine levels, to assess disease course as prognosis and to predict regulators in patients with LVV using the blood profiles of multiple cytokines/chemokines. This retrospective analysis comprised 35 LVV patients whose blood were collected, and multiplex cytokine/chemokine analysis with 28 analytes was performed. The differences of cytokines/chemokines corresponding disease status, upstream regulator analysis, pathway analysis and cluster analysis were conducted using the cytokines/chemokines profile. Relapse-free survival rate was calculated with Kaplan-Meier analysis in the classified clusters. In the robust analysis, IL-4, CCL2/MCP-1, TNFSF13/APRIL, TNFSF13B/BAFF, CHI3L1 and VEGF-A levels were significantly changed after treatment. Untreated LVV patients demonstrated activation of NFκB-related molecules and these patients are potentially treated with JAK/STAT inhibitors, anti-TNF-α inhibitors and IL-6 inhibitors. Cluster analysis in active LVV patients revealed two clusters including one with high blood levels of IL-1β, IL-6, IL-17, IL-23 and CCL20/MIP-3. A subgroup of the LVV patients showed activated IL-17 signature with high relapse frequency, and JAK/TyK2 inhibitors and IFN-γ inhibitors were detected as potentially upstream inhibitors. Blood cytokine/chemokine profiles would be useful for prediction of relapse and potentially contributes to establish therapeutic strategy as precision medicine in LVV patients.

Lupus-induced autoimmune chloride channelopathy-like myotonia congenita, successfully treated with immunosuppression.
Nobuya Abe, Michihito Kono, Ikuko Iwata, Tatsuya Atsumi
Rheumatology (Oxford, England), 61, 1, e4-e5, 2021年12月24日, ［査読有り］, ［責任著者］, ［国際誌］
英語

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.

The assessment of left heart disease in patients with systemic sclerosis and pulmonary hypertension.
Keita Ninagawa, Masaru Kato, Hiroshi Ohira, Satonori Tsuneta, Hiroyuki Iwano, Michihito Kono, Yuichiro Fujieda, Kenji Oku, Ichizo Tsujino, Tatsuya Atsumi
Clinical and experimental rheumatology, 2021年05月12日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) is of clinical significance owing to its poor outcome. One of the explanations for the outcome is the co-presence of left heart disease (LHD). The aim of this study is to assess LHD phenotype in patients with SSc and pulmonary hypertension (PH). METHODS: This study included consecutive patients with SSc who underwent right heart catheterisation to diagnose PAH. Heart failure with preserved ejection fraction (HFpEF) was evaluated according to the recommendation of 6th WSPH and to the Framingham criteria. RESULTS: In total, 76 patients were enrolled in this study. Of them, 42 had PH (mPAP >20 mmHg) with a normal left ventricle ejection fraction (≥50%). Among the 42 patients, four and three patients were classified "HFpEF not excluded" and "HFpEF confirmed" whereas 10 had a clinical diagnosis of HFpEF according to 6th WSPH and Framingham criteria, respectively. These differences were due mainly to relatively low PAWP (<13 mmHg). By a combination of ROC curve and logistic regression analyses, left atrial dimension and left ventricular end-diastolic volume index assessed with echocardiography and cardiac MRI, respectively, had significantly higher predictive values for detecting the complication of HFpEF rather than PAWP. CONCLUSIONS: Morphological evaluation using echocardiography and cardiac MRI, compared with haemodynamic evaluation by PAWP, may better reflect the copresence of LHD phenotype in patients with SSc and PH. Our data would also indicate a limited elevation of PAWP in patients with SSc, PH and HFpEF.

ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1.
Masataka Umeda, Nobuya Yoshida, Ryo Hisada, Catalina Burbano, Seo Yeon K Orite, Michihito Kono, Vasileios C Kyttaris, Suzanne Krishfield, Caroline A Owen, George C Tsokos
Proceedings of the National Academy of Sciences of the United States of America, 118, 18, 2021年05月04日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The a disintegrin and metalloproteinase (ADAM) family of proteinases alter the extracellular environment and are involved in the development of T cells and autoimmunity. The role of ADAM family members in Th17 cell differentiation is unknown. We identified ADAM9 to be specifically expressed and to promote Th17 differentiation. Mechanistically, we found that ADAM9 cleaved the latency-associated peptide to produce bioactive transforming growth factor β1, which promoted SMAD2/3 phosphorylation and activation. A transcription factor inducible cAMP early repressor was found to bind directly to the ADAM9 promoter and to promote its transcription. Adam9-deficient mice displayed mitigated experimental autoimmune encephalomyelitis, and transfer of Adam9-deficient myelin oligodendrocyte globulin-specific T cells into Rag1 -/- mice failed to induce disease. At the translational level, an increased abundance of ADAM9 levels was observed in CD4+ T cells from patients with systemic lupus erythematosus, and ADAM9 gene deletion in lupus primary CD4+ T cells clearly attenuated their ability to differentiate into Th17 cells. These findings revealed that ADAM9 as a proteinase provides Th17 cells with an ability to activate transforming growth factor β1 and accelerates its differentiation, resulting in aberrant autoimmunity.

胸部CTでの定量的手法による1群又は3群強皮症性肺高血圧症の評価　　　　　　　　　　　　　　　
蜷川 慶太, 加藤 将, 河野 通仁, 藤枝 雄一郎, 大平 洋, 奥 健志, 杉森 博行, 辻野 一三, 渥美 達也
日本肺高血圧・肺循環学会学術集会・日本小児肺循環研究会プログラム・抄録集, 6回・27回, 41, 41, 日本肺高血圧・肺循環学会・日本小児肺循環研究会, 2021年05月
日本語

関節リウマチ患者におけるサラゾスルファピリジンによるニューモシスティス肺炎の予防効果　　　　　　　　　　　　　　　
阿部 靖矢, 河野 通仁, 奥 健志
感染症学雑誌, 95, 臨増, 226, 226, (一社)日本感染症学会, 2021年04月
日本語

血清サイトカイン・ケモカインのマルチプレックス解析を用いたTAFRO症候群における新規病態関連分子の検索　　　　　　　　　　　　　　　
垂水 政人, 阿部 靖矢, 河野 通仁, 藤枝 雄一郎, 加藤 将, 奥 健志, アメングアル・オルガ, 渥美 達也
日本リウマチ学会北海道・東北支部学術集会抄録集, 30回, 58, 58, (一社)日本リウマチ学会-北海道・東北支部, 2021年02月
日本語

Amino Acid Metabolism in Lupus.
Michihito Kono, Nobuya Yoshida, George C Tsokos
Frontiers in immunology, 12, 623844, 623844, 2021年, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, T cell metabolism is central to cell proliferation, survival, differentiation, and aberrations have been linked to the pathophysiology of systemic autoimmune diseases. Besides glycolysis and fatty acid oxidation/synthesis, amino acid metabolism is also crucial in T cell metabolism. It appears that each T cell subset favors a unique metabolic process and that metabolic reprogramming changes cell fate. Here, we review the mechanisms whereby amino acid transport and metabolism affects T cell activation, differentiation and function in T cells in the prototype systemic autoimmune disease systemic lupus erythematosus. New insights in amino acid handling by T cells should guide approaches to correct T cell abnormalities and disease pathology.

Morbidity and mortality in antiphospholipid syndrome based on cluster analysis: a 10-year longitudinal cohort study.
Yusuke Ogata, Yuichiro Fujieda, Masanari Sugawara, Taiki Sato, Naoki Ohnishi, Michihito Kono, Masaru Kato, Kenji Oku, Olga Amengual, Tatsuya Atsumi
Rheumatology (Oxford, England), 60, 3, 1331, 1337, 2020年09月18日, ［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.

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］, ［責任著者］, ［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.

Serine/threonine phosphatase PP2A is essential for optimal B cell function.
Esra Meidan, Hao Li, Wenliang Pan, Michihito Kono, Shuilian Yu, Vasileios C Kyttaris, Christina Ioannidis, Noe Rodriguez Rodriguez, Jose C Crispin, Sokratis A Apostolidis, Pui Lee, John Manis, Amir Sharabi, Maria G Tsokos, George C Tsokos
JCI insight, 5, 5, 2020年03月12日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro-activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus display increased PP2A activity. To understand the contribution of PP2A to B cell function, we generated a Cd19CrePpp2r1afl/fl (flox/flox) mouse which lacks functional PP2A only in B cells. Flox/flox mice displayed reduced spontaneous germinal center formation and decreased responses to T cell-dependent and T-independent antigens, while their B cells responded poorly in vitro to stimulation with an anti-CD40 antibody or CpG in the presence of IL-4. Transcriptome and metabolome studies revealed altered nicotinamide adenine dinucleotide (NAD) and purine/pyrimidine metabolism and increased expression of purine nucleoside phosphorylase in PP2A-deficient B cells. Our results demonstrate that PP2A is required for optimal B cell function and may contribute to increased B cell activity in systemic autoimmunity.

MicroRNA-9 ameliorates destructive arthritis through down-regulation of NF-κB1-RANKL pathway in fibroblast-like synoviocytes.
Wen Shi Lee, Shinsuke Yasuda, Michihiro Kono, Yuki Kudo, Sanae Shimamura, Michihito Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Tomohiro Shimizu, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi
Clinical immunology (Orlando, Fla.), 212, 108348, 108348, 2020年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We investigated the effect of miR-9 on fibroblast-like synoviocytes (FLS) from RA patients and animal arthritis model. The binding of miR-9 to NF-κB1 3'UTR was analyzed by luciferase reporter assay and immunoprecipitation. ChIP assay and luciferase promoter assay were performed to identify the binding of NF-κB1 to RANKL promoter and its activity. FLS were treated with miR-9/anti-miR-9 to evaluate cell proliferation and the expression of RANKL. Therapeutic effect of intra-articular miR-9 was evaluated in type-II collagen-induced arthritis in rats. miR-9 bound to the 3'-UTR of NF-κB1 and downregulated NF-κB1. NF-κB1 bound to RANKL promoter and increased the promoter activity of RANKL. RANKL was downregulated by miR-9. Proliferation of FLS was increased by miR-9 inhibitor. miR-9 dampened experimental arthritis by lowering inflammatory state, reducing RANKL and osteoclasts formation. Our findings revealed miR-9-NF-κB1-RANKL pathway in RA-FLS, further, miR-9 ameliorated inflammatory arthritis in vivo which propose therapeutic implications of miR- 9 in RA.

Right ventricular dimension index by cardiac magnetic resonance for prognostication in connective tissue diseases and pulmonary hypertension.
Nobuya Abe, Masaru Kato, Michihito Kono, Yuichiro Fujieda, Hiroshi Ohira, Ichizo Tsujino, Noriko Oyama-Manabe, Kenji Oku, Toshiyuki Bohgaki, Shinsuke Yasuda, Tatsuya Atsumi
Rheumatology (Oxford, England), 59, 3, 622, 633, 2020年03月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Pulmonary hypertension (PH) in patients with CTD is a heterogeneous condition affected by left heart disease, chronic lung disease and thromboembolism as well as pulmonary vascular disease. Recent studies using cardiac magnetic resonance (CMR) have shown that right ventricular dysfunction is predictive for mortality in patients with PH, but limited to pulmonary arterial hypertension. This study aimed to analyse prognostic factors in PH-CTD. METHODS: This retrospective analysis comprised 84 CTD patients, including SSc, who underwent both CMR and right heart catheterization from 2008 to 2018. Demographics, laboratory findings, and haemodynamic and morphological parameters were extracted. The prognostic value of each parameter was evaluated by multivariate analysis using covariables derived from propensity score to control confounding factors. RESULTS: Of 84 patients, 65 had right heart catheterization-confirmed PH (54 pulmonary arterial hypertension, 11 non-pulmonary arterial hypertension). Nine out of these PH patients died during a median follow-up period of 25 months. In 65 patients with PH, right ventricular end-diastolic dimension index (RVEDDI) evaluated by CMR was independently associated with mortality (hazard ratio 1.24; 95% CI: 1.08-1.46; P = 0.003). In a receiver operating characteristic analysis, RVEDDI highly predicted mortality, with area under the curve of 0.87. The 0.5-2-year follow-up data revealed that RVEDDI in both survivors and non-survivors did not significantly change over the clinical course, leading to the possibility that an early determination of RVEDDI could predict the prognosis. CONCLUSION: RVEDDI simply evaluated by CMR could serve as a significant predictor of mortality in PH-CTD. A further validation cohort study is needed to confirm its usability.

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01月10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.

T cell Metabolism in Lupus.
Milena Vukelic, Michihito Kono, George C Tsokos
Immunometabolism, 2, 2, 2020年, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Abnormal T cell responses are central to the development of autoimmunity and organ damage in systemic lupus erythematosus. Following stimulation, naïve T cells undergo rapid proliferation, differentiation and cytokine production. Since the initial report, approximately two decades ago, that engagement of CD28 enhances glycolysis but PD-1 and CTLA-4 decrease it, significant information has been generated which has linked metabolic reprogramming with the fate of differentiating T cell in health and autoimmunity. Herein we summarize how defects in mitochondrial dysfunction, oxidative stress, glycolysis, glutaminolysis and lipid metabolism contribute to pro-inflammatory T cell responses in systemic lupus erythematosus and discuss how metabolic defects can be exploited therapeutically.

Metabolic control of T cells in autoimmunity.
Kono M, Yoshida N, Tsokos GC
Current opinion in rheumatology, 32, 2, 192, 199, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE OF REVIEW: Th1, Th17, and Treg cells play distinct roles in autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. During the last 5 years we have learned that T-cell metabolism affects cell survival, differentiation and fate of T cells. RECENT FINDINGS: We highlight recent studies which have reported on T-cell metabolism in autoimmune diseases, differences in cellular metabolisms in T-cell subsets among various diseases and transcription factors which control the expression and function of central metabolic enzymes. SUMMARY: Distinct metabolic processes control the function of T-cell subsets in autoimmune disease and known transcription factors control the activity of metabolic enzymes. The revealed insights into the metabolic events of immune cells offer opportunities for new therapeutic approaches.

長期間経過していた原発性Sjoegren症候群に合併した血栓性血小板減少性紫斑病(TTP)の一例　　　　　　　　　　　　　　　
篠原 陸斗, 加藤 将, 渥美 達也, 菅原 正成, 吉村 大, 麻生 邦之, 佐藤 太貴, 蜷川 慶太, 阿部 靖矢, 狩野 皓平, 下山 修平, 尾形 裕介, 大西 直樹, 河野 通仁, 藤枝 雄一郎, 奥 健志, 保田 晋助
日本リウマチ学会北海道・東北支部学術集会抄録集, 29回, 85, 85, (一社)日本リウマチ学会-北海道・東北支部, 2019年11月
日本語

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, Yasuda S, Atsumi T
Lupus, 28, 13, 1577, 1582, 2019年11月, ［査読有り］

Reduced diffusing capacity for carbon monoxide predicts borderline pulmonary arterial pressure in patients with systemic sclerosis.
Ninagawa K, Kato M, Nakamura H, Abe N, Kono M, Fujieda Y, Oku K, Yasuda S, Ohira H, Tsujino I, Atsumi T
Rheumatology international, 39, 11, 1883, 1887, 2019年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20 mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right heart catheterization (RHC) in our hospital during 2010-2018. Following variables were assessed for performance to predict mPAP ≥ 25 mmHg or > 20 mmHg; anti-centromere or U1-RNP antibody, plasma BNP level, serum urate level, right axis deviation, forced vital capacity (FVC)/diffusing capacity for carbon monoxide (DLCO) ratio, and tricuspid regurgitation velocity. Of 58 patients enrolled in this study, 24 had mPAP of ≥ 25 mmHg and 9 had mPAP of 21-24 mmHg. Among variables tested, only FVC/DLCO elevated similarly in patients with mPAP of ≥ 25 mmHg (median 2.5) and those with mPAP of 21-24 mmHg (median 2.5) compared to those with mPAP of ≤ 20 mmHg (median 1.5). Given the particularly good correlation between DLCO and mPAP of > 20 mmHg, each variable was weighted according to its odds ratio and the total weighted score was calculated. The total weighted score exhibited a good predictive performance for mPAP of > 20 mmHg with its sensitivity of 87.5% and specificity of 92%. Among conventional risk factors for PAH, decreased DLCO may predict mPAP > 20 mmHg with priority in SSc patients. Weighting DLCO may improve the performance of screening algorithm for early SSc-PAH.

Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation.
Kono M, Maeda K, Stocton-Gavanescu I, Pan W, Umeda M, Katsuyama E, Burbano C, Orite SYK, Vukelic M, Tsokos MG, Yoshida N, Tsokos GC
JCI insight, 4, 12, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Th1 and Th17 are important in the pathogenesis of autoimmune diseases and they depend on glycolysis as a source of energy. T cell antigen receptor signaling phosphorylates a serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), and promotes glycolysis. Based on these findings we hypothesized that CaMK4 promotes glycolysis. Camk4-deficient CD4+ T cells and cells treated with a CaMK4 inhibitor had less glycolysis compared with their counterparts. Pull-down of CaMK4 and mass spectrometry identified pyruvate kinase muscle isozyme (PKM), the final rate-limiting enzyme in glycolysis, as a binding partner. Coimmunoprecipitation and Western blotting showed that CaMK4 interacts directly with PKM2. Camk4-deficient CD4+ T cells displayed decreased pyruvate kinase activity. Silencing or pharmacological inhibition of PKM2 reduced glycolysis and in vitro differentiation to Th1 and Th17 cells, while PKM2 overexpression restored Th17 cell differentiation. Treatment with a PKM2 inhibitor ameliorated experimental autoimmune encephalomyelitis and CD4+ T cells treated with PKM2 inhibitor or Pkm2-shRNA caused limited disease activity in an adoptive cell transfer model of experimental autoimmune encephalomyelitis. Our data demonstrate that CaMK4 binds to PKM2 and promotes its activity, which is requisite for Th1 and Th17 differentiation in vitro and in vivo. PKM2 represents a therapeutic target for T cell-dependent autoimmune diseases.

Glutaminase 1 Inhibition Reduces Glycolysis and Ameliorates Lupus-like Disease in MRL/lpr Mice and Experimental Autoimmune Encephalomyelitis.
Kono M, Yoshida N, Maeda K, Suárez-Fueyo A, Kyttaris VC, Tsokos GC
Arthritis & rheumatology (Hoboken, N.J.), 2019年06月, ［査読有り］

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

Anti-TIF1γ antibody predicted malignancy of thymic tumor with dermatomyositis as an "autoimmune tumor marker": A case report.
Karino K, Fujieda Y, Kawamura T, Abe N, Shimoyama S, Kono M, Kato M, Yasuda S, Atsumi T
Medicine, 97, 49, e13563, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: An association between inflammatory myopathy and malignancy has been recognized particularly in patients positive for anti-transcription intermediary factor 1γ (TIF1γ) antibody. We report a case of anti-TIF1γ antibody positive dermatomyositis (DM) associated with thymic carcinoma which radiographically mimicked benign tumor. PATIENT CONCERNS: A 72-year-old man presented typical characteristic cutaneous manifestations and proximal muscle weakness with elevated levels of myogenic enzymes. An anterior mediastinal tumor was detected by computed tomography (CT) scan and radiographically assessed to be benign with distinct borders and little enhancement. DIAGNOSES: DM with anti-TIF1γ antibody and thymic carcinoma. INTERVENTIONS: Thymic carcinoma was completely resected by surgery. DM was induced into remission with glucocorticoid treatment. OUTCOMES: The serum level of myogenic enzyme remained within normal range under low-dose glucocorticoid maintenance. No evidence of carcinoma recurrence with CT scan was observed at 1-year follow up. LESSONS: The present case indicated that anti-TIF1γ antibody would play a role as the "autoimmune tumor marker" in patients with inflammatory myopathy.

Decreased Expression of Serine/Arginine-Rich Splicing Factor 1 in T Cells From Patients With Active Systemic Lupus Erythematosus Accounts for Reduced Expression of RasGRP1 and DNA Methyltransferase 1.
Michihiro Kono, Takashi Kurita, Shinsuke Yasuda, Michihito Kono, Yuichiro Fujieda, Toshiyuki Bohgaki, Takayuki Katsuyama, George C Tsokos, Vaishali R Moulton, Tatsuya Atsumi
Arthritis & rheumatology (Hoboken, N.J.), 70, 12, 2046, 2056, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: T cells from systemic lupus erythematosus (SLE) patients have reduced protein levels of RasGRP1, a guanine nucleotide exchange factor for Ras, and increased transcript of alternatively spliced (AS) forms lacking exon 11. Serine/arginine-rich splicing factor 1 (SRSF1) binds pre-messenger RNA (pre-mRNA) to regulate AS forms of several genes, including CD3ζ in SLE T cells. This study was undertaken to assess whether SRSF1 controls the expression of RasGRP1 in T cells from patients with SLE. METHODS: We studied T cells from 45 SLE patients and 18 healthy subjects. Expression levels of SRSF1, wild-type (WT) RasGRP1, and DNA methyltransferase 1 (DNMT1) were assessed by quantitative polymerase chain reaction. Direct binding of SRSF1 to exon 11 of RasGRP1 mRNA was evaluated with an oligonucleotide-protein pulldown assay. Healthy T cells and SLE T cells were treated with SRSF1-specific small interfering RNA or SRSF1 expression vector, respectively, and then evaluated for mRNA/protein expression. RESULTS: SRSF1 expression levels were significantly lower in T cells from SLE patients compared to those from healthy subjects, and correlated inversely with disease activity and positively with levels of RasGRP1-WT and DNMT1. SRSF1 bound directly to exon 11 of RasGRP1 mRNA. Silencing of SRSF1 in human T cells led to increased ratios of RasGRP1-AS to RasGRP1-WT and decreased levels of RasGRP1 protein, whereas overexpression of SRSF1 in SLE T cells caused recovery of RasGRP1, which in turn induced DNMT1/interleukin-2 expression. CONCLUSION: SRSF1 controls the alternative splicing of RasGRP1 and subsequent protein expression. Our findings extend evidence that alternative splicing plays a central role in the aberrant T cell function in patients with SLE by controlling the expression of multiple genes.

Ectopic RASGRP2 (CalDAG-GEFI) expression in rheumatoid synovium contributes to the development of destructive arthritis.
Hiroyuki Nakamura, Sanae Shimamura, Shinsuke Yasuda, Michihito Kono, Michihiro Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tomohiro Shimizu, Norimasa Iwasaki, Tatsuya Atsumi
Annals of the rheumatic diseases, 77, 12, 1765, 1772, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA. METHODS: The expression of RASGRPs mRNA was quantified by a real-time PCR assay in FLS isolated from synovial tissue samples. RASGRP2 protein was also evaluated immunohistochemically. Then, we transiently transfected FLS with RASGRP2 expression vector and assessed their proliferation, adhesion, migration and invasion by cellular functional assays and downstream signalling activation using immunoblot. Finally, the therapeutic effect of RASGRP2 silencing was evaluated in type-II collagen-induced arthritis rats. RESULTS: RASGRP2 was abundantly expressed in FLS from RA synovium, whereas scarcely found in those from osteoarthritis. Expression of RASGRP2 in RA-FLS was enhanced by transforming growth factor-beta. RASGRP2 activated RAP-1, subsequently affecting nuclear factor kappa-light-chain-enhancer of activated B cells pathway and actin dynamics in FLS. RASGRP2-overexpressed FLS had increased abilities of adhesion, migration and interleukin (IL)-6 production. Silencing of RASGRP2 using the intra-articular injection of Rasgrp2-specific siRNAs dampened experimental arthritis in rats by inhibiting pannus formation. CONCLUSIONS: RASGRP2 was identified to be involved in the pathogenesis of RA by promoting adhesion, migration and IL-6 production from FLS, proposed as a potential novel non-immunosuppressive therapeutic target for RA.

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, Taylor and Francis Ltd, 2018年09月03日
英語, 研究論文（学術雑誌）

Quantification of hand synovitis in rheumatoid arthritis: Arterial mask subtraction reinforced with mutual information can improve accuracy of pixel-by-pixel time–intensity curve shape analysis in dynamic MRI
Yuto Kobayashi, Tamotsu Kamishima, Hiroyuki Sugimori, Shota Ichikawa, Atsushi Noguchi, Michihito Kono, Toshitake Iiyama, Kenneth Sutherland, Tatsuya Atsumi
Journal of Magnetic Resonance Imaging, 48, 3, 687, 694, 2018年09月, ［査読有り］
研究論文（学術雑誌）

Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation.
Kono M, Yoshida N, Maeda K, Skinner NE, Pan W, Kyttaris VC, Tsokos MG, Tsokos GC
Proceedings of the National Academy of Sciences of the United States of America, 115, 37, 9288, 9293, 2018年09月, ［査読有り］

CaMK4 compromises podocyte function in autoimmune and nonautoimmune kidney disease.
Kayaho Maeda, Kotaro Otomo, Nobuya Yoshida, Mones S Abu-Asab, Kunihiro Ichinose, Tomoya Nishino, Michihito Kono, Andrew Ferretti, Rhea Bhargava, Shoichi Maruyama, Sean Bickerton, Tarek M Fahmy, Maria G Tsokos, George C Tsokos
The Journal of clinical investigation, 128, 8, 3445, 3459, 2018年08月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Podocyte malfunction occurs in autoimmune and nonautoimmune kidney disease. Calcium signaling is essential for podocyte injury, but the role of Ca2+/calmodulin-dependent kinase (CaMK) signaling in podocytes has not been fully explored. We report that podocytes from patients with lupus nephritis and focal segmental glomerulosclerosis and lupus-prone and lipopolysaccharide- or adriamycin-treated mice display increased expression of CaMK IV (CaMK4), but not CaMK2. Mechanistically, CaMK4 modulated podocyte motility by altering the expression of the GTPases Rac1 and RhoA and suppressed the expression of nephrin, synaptopodin, and actin fibers in podocytes. In addition, it phosphorylated the scaffold protein 14-3-3β, which resulted in the release and degradation of synaptopodin. Targeted delivery of a CaMK4 inhibitor to podocytes preserved their ultrastructure, averted immune complex deposition and crescent formation, and suppressed proteinuria in lupus-prone mice and proteinuria in mice exposed to lipopolysaccharide-induced podocyte injury by preserving nephrin/synaptopodin expression. In animals exposed to adriamycin, podocyte-specific delivery of a CaMK4 inhibitor prevented and reversed podocyte injury and renal disease. We conclude that CaMK4 is pivotal in immune and nonimmune podocyte injury and that its targeted cell-specific inhibition preserves podocyte structure and function and should have therapeutic value in lupus nephritis and podocytopathies, including focal segmental glomerulosclerosis.

Interferon-inducible Mx1 protein is highly expressed in renal tissues from treatment-naïve lupus nephritis, but not in those under immunosuppressive treatment.
Shimizu Y, Yasuda S, Kimura T, Nishio S, Kono M, Ohmura K, Shimamura S, Kono M, Fujieda Y, Kato M, Oku K, Bohgaki T, Fukasawa Y, Tanaka S, Atsumi T
Modern rheumatology, 28, 4, 661, 669, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The aim of this study was to clarify the consequences of Mx1, one of the IFN-inducible proteins, in the peripheral blood as well as in renal tissues in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Mx1 protein concentrations in (PBMCs) from 18 SLE patients mostly in their stable disease status, 11 IgA nephropathy (IgAN) patients, 5 ANCA-associated vasculitis (AAV) patients and 16 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Mx1 expression in renal specimens from 18 patients with lupus nephritis (LN), 18 with IgAN and 10 with AAV were evaluated using immunohistochemistry. RESULTS: Mx1 protein concentrations in lysates of PBMCs were significantly higher in SLE patients compared with those in other three groups. Mx1-positive area in renal tissues was significantly dominant in both glomeruli and renal tubules of LN compared with other renal diseases. Renal Mx1 protein levels were lower in LN after immunosuppressive treatment, compared with those from immunosuppressant-naïve patients. CONCLUSION: Mx1 levels were upregulated in lupus peripheral blood even when their disease activities were stable. On the other hand, Mx1 was highly expressed in kidneys from patients with LN before treatment, which was decreased after immunosuppressive treatment. These results suggest that Mx1 is a potential marker for the diagnosis of SLE in the peripheral blood and also for the activity of lupus nephritis in the kidney.

SLAMF1 engagement inhibits T cell-B cell interaction and diminishes IL-6 production and plasmablast differentiation in systemic lupus erythematosus.
Karampetsou MP, Comte D, Suárez-Fueyo A, Katsuyama E, Yoshida N, Kono M, Kyttaris VC, Tsokos GC
Arthritis & rheumatology (Hoboken, N.J.), 71, 1, 99, 108, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Signaling lymphocytic activation molecule family member 1 (SLAMF1) homophilic interactions promote immunoglobulin production and T cell-B cell cross-talk. SLAMF1 is overexpressed on T and B cells in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the role of SLAMF1 monoclonal antibody (mAb) in modulating T cell-B cell interaction and B cell activation. METHODS: Anti-IgM-prestimulated naive or total B cells from either healthy donors or patients with SLE were cocultured with autologous T cells under CD3/CD28 stimulation, in the presence or absence of the SLAMF1 mAb. Naive B cells were stimulated with anti-IgM and CD40L in the presence of the SLAMF1 antibody. Cytokine production by CD4+ T cells and B cells was examined by flow cytometry and/or quantitative polymerase chain reaction. Plasmablast formation and T cell and B cell conjugates were assessed by flow cytometry. IgG and antinuclear antibody production was determined by enzyme-linked immunosorbent assay. RESULTS: SLAMF1 ligation in a human peripheral blood T cell-B cell culture system reduced the following in both healthy controls and patients with SLE: conjugate formation, interleukin-6 (IL-6) production by B cells, IL-21 and IL-17A production by T cells, and Ig and autoantibody production. Whereas the SLAMF1 mAb directly affected the function of isolated peripheral B cells by decreasing IL-6 and Ig production in vitro, it did not affect cytokine production by isolated T cells stimulated in vitro. CONCLUSION: The SLAMF1 antibody inhibits T cell-B cell interaction and suppresses B cell cytokine production and differentiation, thereby acting as a potential therapeutic tool in the treatment of patients with SLE.

Tocilizumab reduced production of systemic sclerosis-related autoantibodies and anti-cyclic citrullinated protein antibodies in two patients with overlapping systemic sclerosis and rheumatoid arthritis
M. Kono, S. Yasuda, M. Kono, T. Atsumi
Scandinavian Journal of Rheumatology, 47, 3, 248, 250, Taylor and Francis Ltd, 2018年05月04日, ［査読有り］
英語

A case of refractory acute sarcoid myopathy successfully treated with intravenous immunoglobulin
M. Kono, M. Kono, S. Jodo
Scandinavian Journal of Rheumatology, 47, 2, 168, 169, Taylor and Francis Ltd, 2018年03月04日, ［査読有り］
英語

Transcriptional factor ICER promotes glutaminolysis and the generation of Th17 cells.
Kono M, Yoshida N, Maeda K, Tsokos GC
Proceedings of the National Academy of Sciences of the United States of America, 115, 10, 2478, 2483, 2018年03月, ［査読有り］

Power Doppler signal calibration in the finger joint between two models of ultrasound machine: a pilot study using a phantom and joints in patients with rheumatoid arthritis
Ryosuke Sakano, Katsumi Saito, Tamotsu Kamishima, Mutsumi Nishida, Tatsunori Horie, Atsushi Noguchi, Michihito Kono, Kenneth Sutherland, Tatsuya Atsumi
ACTA RADIOLOGICA, 58, 10, 1238, 1244, 2017年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Palisaded neutrophilic and granulomatous dermatitis as a novel cause of hypercalcemia A case report
Michihito Kono, Tomoka Hasegawa, So Nagai, Toshio Odani, Kazumasa Akikawa, Yukiko Nomura, Hidetsugu Sato, Keisuke Kikuchi, Norio Amizuka, Hideaki Kikuchi
MEDICINE, 96, 21, e6968, 2017年05月, ［査読有り］
英語, 研究論文（学術雑誌）

関節リウマチにおける手の滑膜炎定量のためのダイナミック造影強調MRIを用いた簡易的なアプローチ 完全自動化した全画素の分析(Simplified Approach to Quantification for Hand Synovitis in Rheumatoid Arthritis Using Dynamic Contrast Enhanced MRI: Full-Automatic Pixel-By-Pixel Analysis)　　　　　　　　　　　　　　　
Kobayashi Yuto, Kamishima Tamotsu, Ichikawa Shota, Sugimori Hiroyuki, Noguchi Atsushi, Kono Michihito, Atsumi Tatsuya
日本放射線技術学会総会学術大会予稿集, 73回, 178, 179, (公社)日本放射線技術学会, 2017年03月
英語

Pixel-by-Pixel Arterial Spin Labeling Blood Flow Pattern Variation Analysis for Discrimination of Rheumatoid Synovitis: A Pilot Study
Taro Sakashita, Tamotsu Kamishima, Hiroyuki Sugimori, Minghui Tang, Atsushi Noguchi, Michihito Kono, Kenneth Sutherland, Tatsuya Atsumi
MAGNETIC RESONANCE IN MEDICAL SCIENCES, 16, 1, 78, 83, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）

Bi-ventricular interplay in patients with systemic sclerosis-associated pulmonary arterial hypertension: Detection by cardiac magnetic resonance
Atsushi Noguchi, Masaru Kato, Michihito Kono, Kazumasa Ohmura, Hiroshi Ohira, Ichizo Tsujino, Noriko Oyama-Manabe, Kenji Oku, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Masaharu Nishimura, Tatsuya Atsumi
MODERN RHEUMATOLOGY, 27, 3, 481, 488, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）

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, 2017年, ［査読有り］
英語, 研究論文（学術雑誌）

AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts
Masaru Kato, Caroline Ospelt, Christoph Kolling, Tomohiro Shimizu, Michihito Kono, Shinsuke Yasuda, Beat A. Michel, Renate E. Gay, Steffen Gay, Kerstin Klein, Tatsuya Atsumi
ONCOTARGET, 7, 39, 64221, 64232, 2016年09月, ［査読有り］
英語, 研究論文（学術雑誌）

ICER is requisite for Th17 differentiation
Nobuya Yoshida, Denis Comte, Masayuki Mizui, Kotaro Otomo, Florencia Rosetti, Tanya N. Mayadas, Jose C. Crispin, Sean J. Bradley, Tomohiro Koga, Michihito Kono, Maria P. Karampetsou, Vasileios C. Kyttaris, Klaus Tenbrock, George C. Tsokos
NATURE COMMUNICATIONS, 7, 12993, 2016年09月, ［査読有り］
英語, 研究論文（学術雑誌）

Engagement of SLAMF3 enhances CD4(+) T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus
Denis Comte, Maria P. Karampetsou, Katalin Kis-Toth, Nobuya Yoshida, Sean J. Bradley, Masayuki Mizui, Michihito Kono, Julie R. Solomon, Vasileios C. Kyttaris, George C. Tsokos
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113, 33, 9321, 9326, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）

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, 2016年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Accurate quantitative assessment of synovitis in rheumatoid arthritis using pixel-by-pixel, time-intensity curve shape analysis
Taro Sakashita, Tamotsu Kamishima, Yuto Kobayashi, Hiroyuki Sugimori, Minghui Tang, Kenneth Sutherland, Atsushi Noguchi, Michihito Kono, Tatsuya Atsumi
BRITISH JOURNAL OF RADIOLOGY, 89, 1061, 20151000, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）

Prognosis and progress in immunotherapies for organ involvements in systemic autoimmune diseases
Shinsuke Yasuda, Michihito Kono, Sanae Shimamura, Takashi Kurita, Toshio Odani, Tatsuya Atsumi
Japanese Journal of Clinical Immunology, 39, 1, 8, 17, Japan Society for Clinical Immunology, 2016年, ［査読有り］
日本語, 研究論文（学術雑誌）

HLA-B52-positive Aortitis with Antineutrophil Cytoplasmic Antibody-associated Vasculitis
Kohei Karino, Michihito Kono
INTERNAL MEDICINE, 55, 23, 3545, 3545, 2016年, ［査読有り］
英語

膠原病 心臓MRIは強皮症性肺高血圧症の予後予測に有用である　　　　　　　　　　　　　　　
野口 淳史, 保田 晋助, 河野 通仁, 加藤 将, 真鍋 徳子, 佐藤 隆博, 辻野 一三, 西村 正治, 渥美 達也
呼吸と循環, 63, 8, S34, S34, (株)医学書院, 2015年08月
日本語

Projectile haemorrhage of a brachial artery in a patient with clinically amyopathic dermatomyositis
Michihito Kono, Shinsuke Yasuda, Toshiyuki Watanabe, Tatsuya Atsumi
RHEUMATOLOGY, 54, 8, 1530, 1531, 2015年08月, ［査読有り］
英語

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, 8, 1536, 1536, 2015年08月, ［査読有り］, ［国際誌］
英語

線維筋痛症・臨床(内科) 急速に進行する視力低下で発症し、多発脳梗塞およびクモ膜下出血で死亡した1剖検例　　　　　　　　　　　　　　　
渡邉 加奈子, 小谷 俊雄, 谷村 瞬, 河野 通仁, 深谷 進司, 竹田 剛, 菊池 英明
日本リウマチ学会総会・学術集会プログラム・抄録集, 59回, 396, 396, (一社)日本リウマチ学会, 2015年03月
日本語

リウマチ性滑膜炎の描出 従来型のコントラスト造影MRIに対する二重標識後待ち時間(PLD)測定を利用したASL画像分析法の利点(Depiction of Rheumatoid Synovitis: Advantage of ASL Imaging Analysis Using Dual Post Labeling Delay(PLD) Settings Over Conventional Contrast Enhanced MRI)　　　　　　　　　　　　　　　
Sakashita Taro, Kamishima Tamotsu, Sugimori Hiroyuki, Tou Meiki, Noguchi Atsushi, Kono Michihito, Atsumi Tatsuya
日本放射線技術学会総会学術大会予稿集, 71回, 185, 185, (公社)日本放射線技術学会, 2015年02月
英語

画素間演算と時間強度曲線の形状分析を用いた関節リウマチにおける滑膜炎の正確な定量評価(Accurate Quantitative Assessment of Synovitis in Rheumatoid Arthritis Using Pixel by Pixel, Time-intensity Curve Shape Analysis)　　　　　　　　　　　　　　　
Sugimori Hiroyuki, Tou Meiki, Noguchi Atsushi, Kono Michihito, Atsumi Tatsuya
日本放射線技術学会総会学術大会予稿集, 71回, 185, 185, (公社)日本放射線技術学会, 2015年02月
英語

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, 2015年02月, ［査読有り］
英語, 研究論文（学術雑誌）

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.

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, 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, 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, 2014年10月, ［査読有り］
英語

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, 2014年10月, ［査読有り］
英語

Decreased Levels of SRSF1 (Serin/Arginine-Rich Splicing Factor1) Induced Lower Levels of RasGRP1 in T Cells from Patients with Systemic Lupus Erythematosus.
Takashi Kurita, Shinsuke Yasuda, Vaishali Moulton, Yuka Shimizu, Michihito Kono, Hideyuki Koide, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Tetsuya Horita, George C. Tsokos, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 66, S1171, S1171, 2014年10月, ［査読有り］
英語

Thrombocytopenia in Primary Antiphospholipid Syndrome Is Related to Arterial Thrombosis
Ikuma Nakagawa, Kenji Oku, Olga Amengual, Ryo Hisada, Eri Sugawara, Kazumasa Ohmura, Tomoko Fukui, Sanae Shimamura, Haruki Shida, Toshiyuki Watanabe, Yuka Shimizu, Michihito Kono, Takashi Kurita, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi
ARTHRITIS & RHEUMATOLOGY, 66, S1, S1, 2014年10月, ［査読有り］
英語

Long-term outcome in Japanese patients with lupus nephritis
M. Kono, S. Yasuda, M. Kato, Y. Kanetsuka, T. Kurita, Y. Fujieda, K. Otomo, T. Horita, K. Oba, M. Kondo, M. Mukai, M. Yanai, Y. Fukasawa, T. Atsumi
LUPUS, 23, 11, 1124, 1132, 2014年10月, ［査読有り］
英語, 研究論文（学術雑誌）

手関節のリウマチ滑膜炎におけるPixel-by-Pixel TIC解析　　　　　　　　　　　　　　　
坂下 太郎, 神島 保, 杉森 博行, 唐 明輝, 河野 通仁, 渥美 達也
日本放射線技術学会雑誌, 70, 9, 965, 965, (公社)日本放射線技術学会, 2014年09月
日本語

多時相造影MRIのTIC解析を用いた滑膜炎抽出
小野 雅人, 神島 保, 杉森 博行, 唐 明輝, 河野 通仁, 渥美 達也
北海道医学雑誌, 89, 1, 93, 93, 北海道医学会, 2014年05月
日本語

Successful treatment with tacrolimus of refractory adult-onset Still's disease
Masashi Ohe, Kenji Oku, Michihito Kono, Toshiyuki Bohgaki
KOREAN JOURNAL OF INTERNAL MEDICINE, 29, 2, 259, 261, 2014年03月, ［査読有り］
英語

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］

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］

[Treatment of rheumatic diseases: current status and future prospective. Topics: II. Immunosuppressant/antirheumatic drugs: 9. Mycophenolate mofetil].
Kono M, Atsumi T
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 100, 10, 2954, 2959, 2011年10月, ［査読有り］

肺梗塞を発症した抗リン脂質抗体症候群合併SLEの1例
野本 博司, 佐藤 力, 河野 通仁, 谷口 聡, 田村 元男, 山根 康昭, 浄土 智, 藤咲 淳
北海道医学雑誌, 84, 5, 404, 404, 北海道医学会, 2009年09月
日本語

TNF阻害剤で寛解導入し得た、強直性脊椎炎に関節リウマチを合併した1例
佐藤 力, 河野 通仁, 野本 博司, 谷口 聡, 田村 元男, 山根 康昭, 浄土 智, 藤咲 淳
北海道医学雑誌, 84, 5, 405, 405, 北海道医学会, 2009年09月
日本語

肺梗塞で再発した抗リン脂質抗体症候群合併SLEの1例　　　　　　　　　　　　　　　
野本 博司, 河野 通仁, 浄土 智, 藤咲 淳
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, 53回・18回, 295, 295, (一社)日本リウマチ学会, 2009年03月
日本語

多彩な末梢神経障害を呈したシェーグレン症候群の一例　　　　　　　　　　　　　　　
河野 通仁, 佐藤 力, 野本 博司, 浄土 智, 藤咲 淳
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, 53回・18回, 349, 349, (一社)日本リウマチ学会, 2009年03月
日本語

急性筋炎型を呈したサルコイドーシスの一例　　　　　　　　　　　　　　　
佐藤 力, 河野 通仁, 野本 博司, 浄土 智, 藤咲 淳
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, 53回・18回, 425, 425, (一社)日本リウマチ学会, 2009年03月
日本語

若年全身性エリテマトーデス患者における睡眠健康状態と精神神経症状との関連性:PLEASURE-Jコホートを用いた検討
吉村大, 吉村大, 藤枝雄一郎, 久田諒, 河野通仁, 磯島咲子, 一瀬邦弘, 岩田恭宜, 奥健志, 金子佳代子, 佐田憲映, 田中良哉, 藤尾圭志, 松下雅和, 宮前多佳子, 村島温子, 中島亜矢子, 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, 69th, 2025年

本邦における血栓性微小血管症を伴う全身性エリテマトーデス患者の特性と臨床所見:ケースシリーズ研究
奥健志, 奥健志, 渥美達也, 河野通仁, 石井智徳, 石井智徳, 町山智章, 松下雅和, 河本敏雄, 河野正憲, 下野明彦, 藤尾圭志, 日本リウマチ学会総会・学術集会プログラム・抄録集, 69th, 2025年

Novel therapeutic strategies targeting abnormal T-cell signaling in systemic lupus erythematosus
Masayuki Mizui, Michihito Kono, Clinical Immunology, 262, 110182, 110182, 2024年05月, ［国際誌］
英語

膠原病患者のニューモシスチス肺炎における定量的CT画像を用いた予後予測
崎山広大, 久田諒, 加藤将, 菅原正成, 清水裕香, 河野通仁, 藤枝雄一郎, アメングアルオルガ, 渥美達也, 日本内科学会雑誌, 113, 2024年

長期観察で血栓症発症を確認しえた産科的抗リン脂質抗体症候群4例の臨床像
井上雄太, 藤枝雄一郎, 安田充孝, 久田諒, 河野通仁, AMENGUAL Olga, 加藤将, 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, 68th, 2024年

抗リン脂質抗体症候群患者における単球/HDLコレステロール比の上昇は血栓性イベント再発リスクを反映する
守谷悠, 久田諒, 河野通仁, 藤枝雄一郎, 加藤将, OLGA Amengual, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 52nd, 2024年

全身性強皮症関連間質性肺疾患(SSc-ILD)に対するシクロホスファミド(IVCY)とニンテダニブ併用療法
沖庸太郎, 加藤将, 鎌田和郎, 久田諒, 河野通仁, 藤枝雄一郎, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 39th, 2024年

呼吸機能検査と運動負荷心エコーを組合わせたPAHスクリーニング
鎌田和郎, 加藤将, 石坂傑, 久田諒, 河野通仁, 藤枝雄一郎, 佐藤隆博, 辻野一三, アメングアル オルガ, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 9th (CD-ROM), 2024年

全身性強皮症における心筋線維化に対するニンテダニブの有効性に関する検討
蜷川慶太, 加藤将, 河野通仁, 藤枝雄一郎, 渥美達也, 日本内科学会雑誌, 112, 2023年

MR Vessel Wall ImagingはSLE患者において神経精神ループスの診断能を向上させる
垂水政人, 藤枝雄一郎, 久田諒, 河野通仁, 加藤将, アメングアルオルガ, 渥美達也, 日本臨床免疫学会総会プログラム・抄録集, 51st, 2023年

Epstein-Barrウイルスの再活性化が原因と考えられたdifficult to treat rheumatoid arthritisの3例
井上雄太, 藤枝雄一郎, 宮本健一, 鎌田和郎, 沖庸太郎, 久田諒, 河野通仁, AMENGUAL Olga, 加藤将, 渥美達也, 日本臨床リウマチ学会プログラム・抄録集, 38th, 2023年

強皮症性肺動脈性高血圧症における2群および3群肺高血圧症スペクトラムの評価法
蜷川慶太, 加藤将, 河野通仁, 藤枝雄一郎, 渥美達也, 日本内科学会雑誌, 111, 2022年

SARS-CoV-2ワクチン接種とホスファチジルセリン依存性抗プロトロンビン抗体価上昇に関する検討
安田充孝, 藤枝雄一郎, 崎山広大, 多田麻里亜, 土田直央, 西野慶, 守谷悠, 河野通仁, 加藤将, アメングアル オルガ, 渥美達也, 日本血栓止血学会誌, 33, 2, 2022年

多発仮性動脈瘤を契機に血管型Ehlers-Danlos症候群と診断された一例
吉村大, 久田諒, 垂水政人, 河野通仁, 藤枝雄一郎, 加藤将, アメングアル オルガ, 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

自己免疫性肺胞蛋白症を合併した全身性エリテマトーデスの一例
鎌田和郎, 久田諒, 沖庸太郎, 小森卓, 崎山広大, 多田麻里亜, 守谷悠, 河野通仁, 藤枝雄一郎, 加藤将, AMENGUAL Olga, 今野哲, 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

定量的CTによる異常肺容積値は全身性強皮症に伴う間質性肺疾患の予後を予測する
多田麻里亜, 加藤将, 崎山広大, 守谷悠, 安田充孝, 久田諒, 河野通仁, 藤枝雄一郎, アメングアル オルガ, 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

筋に限局した小型血管炎の2例
守谷悠, 藤枝雄一郎, 多田麻里亜, 崎山広大, 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

SARS-CoV-2mRNAワクチン接種後の抗リン脂質抗体価の変化に関する検討
安田充孝, 藤枝雄一郎, 崎山広大, 多田麻里亜, 守谷悠, 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

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, 久田諒, 河野通仁, 藤枝雄一郎, アメングアル オルガ, 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

肺静脈病変に特徴的な胸部CT所見を有する全身性強皮症患者の循環呼吸動態
守谷悠, 加藤将, 蜷川慶太, 久田諒, 河野通仁, 藤枝雄一郎, 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

全身性エリテマトーデスの維持期における寛解達成及び再燃予測因子に関する検討
竹山脩平, 河野通仁, 久田諒, 藤枝雄一郎, 加藤将, アメングアル オルガ, 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

成人発症スティル病との鑑別を要した皮下脂肪織炎様T細胞リンパ腫の一例
加地紫苑, 多田麻里亜, 鎌田和郎, 沖庸太郎, 崎山広大, 安田充孝, 守谷悠, 久田諒, 河野通仁, 藤枝雄一郎, 加藤将, AMENGUAL Olga, 小野澤真弘, 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

神経精神障害を有する全身性エリテマトーデスの診断におけるMR Vessel Wall Imagingの有用性の検討
垂水政人, 藤枝雄一郎, 久田諒, 河野通仁, 加藤将, アメングアル オルガ, 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

単純X線検査で異常を示さない早期脊椎関節炎・関節リウマチの全身MRI所見
小住由衣, 麻生邦之, 加藤将, 久田諒, 河野通仁, 藤枝雄一郎, アメングアル オルガ, 神島保, 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, アメングアル オルガ, 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, 日本臨床リウマチ学会プログラム・抄録集, 37th, 2022年

胸椎病変を認めたSAPHO症候群の1例
沖庸太郎, 久田諒, 鎌田和郎, 崎山広大, 多田麻里亜, 守谷遥, 河野通仁, 藤枝雄一郎, 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

PVODに関連した胸部CT所見を有する強皮症患者の循環呼吸動態
守谷悠, 加藤将, 蜷川慶太, 河野通仁, 藤枝雄一郎, 佐藤隆博, 辻野一三, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022年

疾患特異的iPS細胞による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, 河野通仁, 藤枝雄一郎, アメングアル オルガ, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022年

強皮症に伴う間質性肺疾患の定量的CTと臨床パラメータの検討
多田麻里亜, 加藤将, 蜷川慶太, 守谷悠, 河野通仁, 藤枝雄一郎, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 7th, 2022年

膠原病 臨床 1)全身性エリテマトーデスの新規治療薬開発の現況
加藤将, 河野通仁, 月刊皮膚科, 1, 1, 2022年

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

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, オルガ アメングアル, 佐藤太貴, 河野通仁, 加藤将, 奥健志, 渥美達也, 日本血栓止血学会誌, 32, 2, 2021年

低補体血症と血清IgG高値はグルココルチコイド漸減中の再燃リスクである
竹山脩平, 河野通仁, 麻生邦之, 狩野皓平, 藤枝雄一郎, 加藤将, 奥健志, 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, 65th, 2021年

肥厚性硬膜炎に硬膜内多発嚢胞を合併したANCA関連血管炎症候群の一例
平石直幹, 垂水政人, 藤枝雄一郎, 河野通仁, 加藤将, 奥健志, 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, 65th, 2021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, 河野通仁, 藤枝雄一郎, AMENGUAL Olga, 奥健志, 渥美達也, 日本肺高血圧・肺循環学会学術集会抄録集(Web), 6th, 2021年

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

関節リウマチ患者におけるサラゾスルファピリジンによるニューモシスティス肺炎の予防効果
阿部靖矢, 河野通仁, 奥健志, 日本化学療法学会雑誌, 69, Supplement-A, 2021年

ループスモデルマウスにおける慢性ストレス誘導性IL-12p40による精神神経病態への影響
阿部靖矢, 阿部靖矢, 奥健志, 藤枝雄一郎, 狩野皓平, 河野通仁, 加藤将, 田中勇希, 村上正晃, 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, 65th, 2021年

ループスモデルマウスにおける慢性ストレス誘導性IL-12/23p40による精神神経病態への影響
阿部靖矢, 阿部靖矢, 藤枝雄一郎, 奥健志, 河野通仁, 田中勇希, 加藤将, 有沼良幸, 佐藤和貴郎, 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, 49th, 2021年

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04月20日, ［国際誌］
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., 英語

単球細胞表面上のプロトロンビン/MHC class II複合体は抗リン脂質抗体の新規対応抗原である
藤枝雄一郎, 大西直樹, 河野通仁, 加藤将, 奥健志, アメングアル オルガ, 荒瀬尚, 渥美達也, 日本血栓止血学会誌, 31, 2, 2020年

低アルカリフォスファターゼ血症を呈するリウマチ性疾患患者の臨床像
加藤将, 蜷川慶太, 河野通仁, 藤枝雄一郎, 奥健志, 保田晋助, 服部敏之, 谷村一秀, 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

イカロス欠損症に合併した関節リウマチに対しアバタセプトを用いて寛解導入した一例
吉村大, 河野通仁, 菅原正成, 蜷川慶太, 柴田悠平, 藤枝雄一郎, 加藤将, 奥健志, アメングアル オルガ, 保田晋助, 山中純子, 岡野翼, 今井耕輔, 森尾友宏, 渥美達也, 日本免疫不全・自己炎症学会総会・学術集会プログラム・抄録集, 3rd, 2020年

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

関節リウマチ患者における深部静脈血栓症発症のリスク評価
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

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

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

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

抗リン脂質抗体症候群におけるプロトロンビン/MHCクラスII分子複合体による抗原提示機構に関する検討
大西直樹, 藤枝雄一郎, 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, 荒瀬尚, 渥美達也, 日本血栓止血学会誌, 30, 2, 2019年

強皮症患者における平均肺動脈圧>20mmHg予測アルゴリズムの作成
蜷川慶太, 加藤将, 中村浩之, 麻生邦之, 佐藤太貴, 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, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

器質化肺炎を合併した抗MDA-5抗体陽性皮膚筋炎の一例
對馬崚太, 蜷川慶太, 麻生邦之, 佐藤太貴, 藤枝雄一郎, 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, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

左椎骨動脈解離を繰り返した全身性エリテマトーデスの一例~Vessel Wall Imagingが導く病態解釈と治療介入~
伊丹久実, 麻生邦之, 蜷川慶太, 佐藤太貴, 藤枝雄一郎, 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, 日本リウマチ学会総会・学術集会プログラム・抄録集, 63rd, 2019年

SLEとの鑑別を要したTAFRO症候群の1例
中村祐哉, 佐藤太貴, 奥健志, 麻生邦之, 蜷川慶太, 河野通仁, 藤枝雄一郎, 加藤将, 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, 63rd, 2019年

多彩な精神・神経症状を呈し,腫瘤性病変との鑑別を要した中枢神経限局性血管炎の1例
野津麟太郎, 吉村大, 藤枝雄一郎, 蜷川慶太, 麻生邦之, 佐藤太貴, 河野通仁, 加藤将, 奥健志, 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, 34th, 2019年

関節リウマチ患者の線維芽細胞様滑膜細胞においてRasGRP4-Ras-MAPキナーゼ経路をファルネシルトランスフェラーゼ阻害剤は阻害する
嶋村抄苗, 保田晋助, 河野通仁, 藤枝雄一郎, 加藤将, 奥健志, 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

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

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

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

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

骨髄異形成/骨髄増殖性腫瘍に合併した大血管炎の一例
菅原正成, 藤枝雄一郎, 吉村大, 麻生邦之, 佐藤太貴, 蜷川慶太, 阿部靖矢, 狩野晧平, 下山修平, 大西直樹, 柴田悠平, 河野通仁, 加藤将, 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

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

ループス腎炎に合併した免疫性血小板減少症に対するミコフェノール酸モフェチルの有効性
狩野皓平, 河野通仁, 麻生邦之, 阿部靖矢, 藤枝雄一郎, 加藤将, 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

Vessel Wall Imagingが脳血管炎の診断に有用だった精神神経ループスの一例
瀬越尚人, 麻生邦之, 藤枝雄一郎, 高橋育子, 佐藤太貴, 蜷川慶太, 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, 日本臨床免疫学会総会プログラム・抄録集, 46th, 2018年

腋窩神経および反回神経麻痺を呈したIgG4関連ニューロパチーの一例
蜷川慶太, 藤枝雄一郎, 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, 日本臨床リウマチ学会プログラム・抄録集, 33rd, 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

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

ダイナミックMRIによる手関節リウマチ滑膜炎の定量化
小林勇渡, 田口愛望, 杉森博之, 神島保, 市川翔太, SUTHERLAND Kenneth, 野口淳史, 河野通仁, 渥美達也, 北海道医学雑誌, 93, 2, 2018年

関節リウマチにおける造影ダイナミックMRIを用いた滑膜炎定量評価
小林 勇渡, 市川 翔太, 神島 保, 杉森 博行, 野口 淳史, 河野 通仁, 渥美 達也, 北海道医学雑誌, 92, 2, 108, 109, 2017年11月
北海道医学会, 日本語

Inducible cAMP Early Repressor Promotes Glycolysis By Inhibiting the Pyruvate Dehydrogenase Phosphatase Catalytic Subunit 2 in Th17 Cells
Michihito Kono, Nobuya Yoshida, Nicole E. Skinner, George C. Tsokos, ARTHRITIS & RHEUMATOLOGY, 69, 2017年10月
英語, 研究発表ペーパー・要旨（国際会議）

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
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
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
英語, 研究発表ペーパー・要旨（国際会議）

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

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
英語, 研究発表ペーパー・要旨（国際会議）

当院における肺高血圧診療連携の実態　　　　　　　　　　　　　　　
澤岡 亜衣, 高村 圭, 瀧本 理子, 松本 宗大, 荻 喬博, 山本 真, 小山 雅之, 河野 通仁, 小谷 俊雄, 深谷 進司, 呼吸と循環, 64, 5, S58, S58, 2016年05月
(株)医学書院, 日本語

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

全身性自己免疫疾患の臓器合併症の予後と免疫治療の進歩
保田 晋助, 河野 通仁, 嶋村 抄苗, 栗田 崇史, 小谷 俊雄, 渥美 達也, 日本臨床免疫学会会誌, 39, 1, 8, 17, 2016年
日本臨床免疫学会, 日本語

粟粒結核による敗血症性ショックで死亡した関節リウマチの1例　　　　　　　　　　　　　　　
渡邉 加奈子, 小谷 俊雄, 谷村 瞬, 河野 通仁, 深谷 進司, 竹田 剛, 菊池 英明, 菊地 慶介, 帯広厚生病院医誌, 18, 59, 63, 2015年12月
帯広厚生病院, 日本語

AAA-Atpase p97-HDAC6 Controlled Poly-Ubiquitin Turnover Regulates Apoptotic and Autophagy-Associated Cell Death in Arthritis
Masaru Kato, Kerstin Klein, Caroline Ospelt, Christoph Kolling, Michihito Kono, Shinsuke Yasuda, Renate E. Gay, Steffen Gay, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 67, 2015年10月
英語, 研究発表ペーパー・要旨（国際会議）

AAA-ATPASE P97 REGULATES APOPTOTIC AND AUTOPHAGY-ASSOCIATED CELL DEATH IN ARTHRITIS
M. Kato, K. Klein, C. Ospelt, C. Kolling, M. Kono, S. Yasuda, R. E. Gay, S. Gay, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 74, 207, 208, 2015年06月
英語, 研究発表ペーパー・要旨（国際会議）

HIGH SERUM LEVELS OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY AND MATRIX METALLOPROTEINASE-3 AT THE TIME OF DIAGNOSIS OF RHEUMATOID ARTHRITIS ARE POSSIBLE PREDICTORS OF FUTURE INITIATION OF BIOLOGICAL AGENTS
M. Kono, T. Odani, K. Hiura, S. Fukayal, K. Oba, T. Takeda, H. Kikuchi, S. Lwaki-Egawa, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 74, 991, 991, 2015年06月
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
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
英語, 研究発表ペーパー・要旨（国際会議）

関節リウマチの治療 生物学的製剤(TNF阻害薬以外) 当科における関節リウマチに対するトシリズマブ休薬後の寛解維持予測因子の検討　　　　　　　　　　　　　　　
野口 淳史, 保田 晋助, 河野 通仁, 菅原 恵理, 久田 諒, 大村 一将, 服部 敏之, 嶋村 抄苗, 中川 育磨, 志田 玄貴, 渡邊 俊之, 清水 裕香, 加藤 将, 奥 健志, 坊垣 暁之, 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, 59回, 324, 324, 2015年03月
(一社)日本リウマチ学会, 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

AAA-Atpase p97 Regulates Autophagy-Associated Cell Death in Arthritis
Masaru Kato, Kerstin Klein, Caroline Ospelt, Christoph Kolling, Michihito Kono, Shinsuke Yasuda, Renate E. Gay, Steffen Gay, Tatsuya Atsumi, ARTHRITIS & RHEUMATOLOGY, 66, S195, S195, 2014年10月
英語, 研究発表ペーパー・要旨（国際会議）

精神神経ループスにおけるMx1の解析
清水 裕香, 保田 晋助, 栗田 崇史, 中川 育磨, 野口 淳史, 志田 玄貴, 渡邊 俊之, 河野 通仁, 奥 健志, 坊垣 暁之, 堀田 哲也, 渥美 達也, 日本臨床免疫学会会誌, 37, 4, 344, 344, 2014年08月
【目的】SLE患者の末梢血T細胞における発現異常分子を明らかにし，病態への関与を検討する．【研究1】方法：対象は活動性SLE患者8例，健常人8例を第1群，非活動性SLE患者6例，健常人6例を第2群とし，末梢血からT細胞を純化，各群で患者および健常人のRNAプールを作製してGeneChipにアプライした．結果：SLE患者では両群に共通してMx1の発現が亢進していた．【研究2】方法：SLE患者33例，健常人22例を対象とし，Mx1のmRNA発現レベルを定量的PCR法で評価した．結果：Mx1のmRNA発現は，有意にSLE患者群において亢進していた（p＜0.0001）．【研究3】方法：NPSLE患者20例，精神神経症状を認めないSLE（non-NPSLE）患者9例を対象とし，血清および髄液Mx1濃度を，ELISA法で測定した．結果：SLE患者における血清，髄液Mx1濃度は正の相関（R＝0.36）を示し，髄液Mx1濃度は血清Mx1濃度と比較し有意に高値（p＜0.05）であった．さらに，NPSLE群の血清Mx1濃度はnon-NPSLE群と比較して高値であった（p＜0.05）．【考察】SLE患者の末梢血ではIFN誘導蛋白が高発現し，活動性とも相関すると報告されており，また，ウイルス性脳炎，多発性硬化症では中枢神経内でMx1が高発現していると報告されている．【結論】Mx1はSLE患者T細胞で高発現し，NPSLEではnon-NPSLEと比較して血清濃度が有意に高かったことから，NPSLEのバイオマーカーとして有用である可能性が示唆された．, 日本臨床免疫学会, 日本語

PAHに伴う心肺病変について考えるシンポジウム 膠原病性肺疾患にPHを合併した症例に対する介入
野口 淳史, 河野 通仁, 保田 晋助, 心臓, 46, 8, 1167, 1170, 2014年08月
症例1は34歳女で、全身性エリテマトーデス、器質化肺炎(OP)に合併した肺動脈性肺高血圧症(PAH)の診断でステロイド大量療法を行い、検査所見や症状は改善したが、2年後に咳嗽、労作時呼吸困難が出現した。PAH再燃と考え、ステロイド大量療法およびシクロフォスファミド間欠静注療法による免疫抑制療法を行い、血管拡張療法としてシルデナフィルとアンブリセンタンを追加した。OP、PAHは改善し、運動耐容能も回復した。症例2は46歳女で、全身性強皮症と診断され、間質性肺病変(ILD)に対して在宅酸素療法、免疫抑制療法を行っていたが、呼吸困難が増悪した。強皮症性ILDに合併した肺高血圧症と診断し、酸素投与に加えシルデナフィルを慎重に開始したところ、血行動態は改善した。ILDは免疫抑制療法の適応になく、増悪を抑制できず低酸素血症が進行して2年後に死亡した。, (公財)日本心臓財団, 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

強皮症 強皮症性肺高血圧症の診断における%肺拡散能/全肺胞気量と心臓MRIの有用性　　　　　　　　　　　　　　　
野口 淳史, 保田 晋助, 河野 通仁, 秋田 佳奈恵, 大村 一将, 神田 真聡, 福井 智子, 中川 育磨, 志田 玄貴, 渡邊 俊之, 清水 裕香, 栗田 崇史, 奥 健志, 坊垣 暁之, 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, 371, 371, 2014年03月
(一社)日本リウマチ学会, 日本語

血管炎 Takayasu arteritisの予後不良因子の検討　　　　　　　　　　　　　　　
大村 一将, 堀田 哲也, 神田 真聡, 秋田 佳奈恵, 福井 智子, 中川 育磨, 野口 淳史, 志田 玄貴, 渡邊 俊之, 清水 裕香, 河野 通仁, 栗田 崇史, 奥 健志, 坊垣 暁之, 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, 413, 413, 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

関節リウマチの関節外病変 関節リウマチに合併する肺病変の変化について　　　　　　　　　　　　　　　
秋田 佳奈恵, 保田 晋助, 大村 一将, 神田 真聡, 中川 育磨, 野口 淳史, 福井 智子, 渡邊 俊之, 志田 玄貴, 河野 通仁, 清水 裕香, 栗田 崇史, 奥 健志, 坊垣 暁之, 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, 460, 460, 2014年03月
(一社)日本リウマチ学会, 日本語

高用量ステロイド投与時に発症した精神神経症状の解析　　　　　　　　　　　　　　　
清水 裕香, 保田 晋助, 神田 真聡, 大村 一将, 秋田 佳奈恵, 福井 智子, 中川 育磨, 野口 淳史, 志田 玄貴, 渡邊 俊之, 河野 通仁, 栗田 崇史, 奥 健志, 坊垣 暁之, 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, 633, 633, 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

多時相造影MRIのTIC解析を用いた滑膜炎抽出
小野雅人, 神島保, 杉森博行, 唐明輝, 河野通仁, 渥美達也, 北海道医学雑誌, 89, 1, 2014年

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
英語, 研究発表ペーパー・要旨（国際会議）

【関節リウマチ-新しい考えかたに基づく実地診療の実践-】 セミナー 関節リウマチの単純X線写真による関節評価と治療方針　　　　　　　　　　　　　　　
河野 通仁, 渥美 達也, Medical Practice, 30, 4, 617, 623, 2013年04月
(株)文光堂, 日本語

リウマチ性疾患の肺病変 膠原病性肺動脈性肺高血圧症26例の臨床像の解析　　　　　　　　　　　　　　　
野口 淳史, 河野 通仁, 嶋村 抄苗, 中川 育磨, 渡邊 俊之, 金塚 雄作, 栗田 崇史, 藤枝 雄一郎, 奥 健志, 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, 287, 287, 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

関節リウマチの治療 生物学的製剤(TNF阻害薬以外) 当科における関節リウマチに対するトシリズマブの有効性について First biologic agentとしての可能性　　　　　　　　　　　　　　　
河野 通仁, 保田 晋助, 嶋村 抄苗, 中川 育磨, 野口 淳史, 渡邊 俊之, 金塚 雄作, 栗田 崇史, 藤枝 雄一郎, 橋本 陶子, 奥 健志, 坊垣 暁之, 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, 422, 422, 2013年03月
(一社)日本リウマチ学会, 日本語

血管炎に伴う肥厚性硬膜炎の6例の検討
高宮宗一朗, 志田玄貴, 秋田佳奈恵, 大村一将, 神田真聡, 中川育磨, 野口淳史, 渡邊俊之, 河野通仁, 栗田崇史, 藤枝雄一郎, 奥健志, 坊垣暁之, 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, 28th, 2013年

自家造血幹細胞移植後にSjoegren症候群を発症した強皮症の1例
野口淳史, 保田晋助, 秋田佳奈恵, 大村一将, 神田真聡, 中川育磨, 志田玄貴, 渡邊俊之, 河野通仁, 栗田崇史, 藤枝雄一郎, 奥健志, 坊垣暁之, 堀田哲也, 渥美達也, 日本シェーグレン症候群学会学術集会プログラム・抄録集, 22nd, 2013年

当科におけるLarge Vessel Vasculitisの予後不良因子の解析
大村一将, 河野通仁, 神田真聡, 秋田佳奈恵, 中川育磨, 野口淳史, 志田玄貴, 渡邊俊之, 栗田崇史, 坊垣暁之, 奥健志, 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, 28th, 2013年

P7-07  抗好中球細胞質抗体関連血管炎における血栓症発症の危険因子についての検討
中川 育磨, 奥 健志, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 渡邊 俊之, 秋田 佳奈恵, 大村 一将, 神田 真聡, 野口 淳史, 志田 玄貴, 河野 通仁, 栗田 崇史, 日本臨床免疫学会会誌, 36, 5, 406b, 406b, 2013年
【背景】抗好中球細胞質抗体関連血管炎（AAV）において，血栓症は重篤な臓器病変の一つである．【目的】AAVにおける血栓症発症の危険因子を明らかにする．【方法】2000年1月から2012年12月の間で当科に入院し，副腎皮質ステロイド単剤あるいは免疫抑制剤との併用で治療を開始した初発のAAV（顕微鏡的多発血管炎，好酸球性多発血管炎性肉芽腫症，多発血管炎性肉芽腫症）の患者56例（女性39例，男性17例）を対象とした．血栓症の発症をエンドポイントとし，患者背景，初診時の疾患活動性，内服薬や動脈硬化促進因子などと血栓症との関連を後ろ向きに解析した．【結果】56例の年齢中央値は66歳（IQR 58-70歳），観察期間中央値は38ヶ月（IQR 11-57.5ヶ月）であった．10例（17.8%）が血栓症を発症し，その内訳は動脈血栓症4例（脳梗塞2例，眼動脈分枝閉塞症1例，網膜中心動脈閉塞症1例），静脈血栓症6例（深部静脈血栓症5例，下大静脈血栓症1例）であった．血栓症の危険因子について，Cox比例ハザードモデルを用いて多変量解析を行い，疾患活動性の指標であるfive factors score (FFS）1点以上（p=0.016），免疫抑制剤の非使用（p=0.010）が抽出された．【結語】初診時でのFFS1点以上は血栓症のリスクであった．免疫抑制剤の使用は，血栓症を予防する可能性が示唆された．
, 日本臨床免疫学会, 日本語

P8-01  当科におけるループス腸炎の臨床的検討
黒木 茜, 栗田 崇史, 坊垣 暁之, 奥 健志, 堀田 哲也, 保田 晋助, 渥美 達也, 神田 真聡, 河野 通仁, 秋田 佳奈恵, 大村 一将, 中川 育磨, 野口 淳史, 志田 玄貴, 渡邊 俊之, 日本臨床免疫学会会誌, 36, 5, 408b, 408b, 2013年
【背景】ループス腸炎は，全身性エリテマトーデス（SLE）患者に生じる腸炎のうち，感染性腸炎が除外され，下痢や腹痛などの臨床症状を呈し，画像上小腸病変を有するものとされる．免疫複合体が小動脈の血管壁に沈着し，血管炎が生じることが原因とされ，局所の虚血による粘膜浮腫や漿膜炎を起こす．ループス腸炎の疫学や病態は依然不明な点も多く，臨床的検討も少ない．
【目的】当科におけるループス腸炎の特徴を明らかにする．
【方法】2008年4月から2013年3月までの間に，当科でループス腸炎と診断された患者を後ろ向きに解析した．
【結果】9名（女性8名，男性1名）のループス腸炎患者が抽出された．ループス腸炎診断時の年齢は33（18-41）歳，SLE発症からループス腸炎診断までの期間は1.9（0-15）年，観察期間は2.1（0.5-5.8）年であった．ループス腸炎の診断時のSLE disease activity indexは15（4-21）であり，腹水貯留5例（56%），胸水貯留2例（22%），膀胱炎を3例（33%）で合併していた．また，9例中3例（33%）で再発し，再発までの期間は，それぞれ5ヶ月，67ヶ月，67ヶ月であった．再発例と非再発例の臨床症状，検査所見を検討したところ，再発例では3例中2例で初発時に結腸，直腸粘膜浮腫を伴っていたが，非再発例では1例も結腸，直腸粘膜浮腫は認めなかった．
【結語】9例のループス腸炎を経験した．初発時に結腸，直腸粘膜浮腫を伴う場合には再発に注意が必要と考えられた．
, 日本臨床免疫学会, 日本語

P9-10  進行性の神経症状を呈した若年女性の結節性多発動脈炎の一例
狩野 皓平, 栗田 崇史, 奥 健志, 坊垣 暁之, 堀田 哲也, 保田 晋助, 渥美 達也, 中川 育磨, 秋田 佳奈恵, 大村 一将, 神田 真聡, 野口 淳史, 志田 玄貴, 渡邊 俊之, 河野 通仁, 日本臨床免疫学会会誌, 36, 5, 421b, 421b, 2013年
 症例は21歳女性．20XX年3月25日から発熱，頭痛と両下肢に紫斑と紅色丘疹が出現した．その数日後には右4,5指の疼痛と運動困難，左下肢のしびれが出現した．4月11日に前医を受診し，下腿の皮膚生検では白血球破砕性血管炎の所見であった．プレドニゾロン（PSL）50 mgで治療が開始されたが皮疹と神経症状は改善せず，精査加療の目的に当科へ入院となった．神経伝導速度検査（NST）では右尺骨神経，左脛骨神経の振幅低下を認めた．下腿紫斑からの皮膚生検を再度行い，真皮下層の小動脈にフィブリノイド壊死を伴う血管炎の所見を認め，結節性多発動脈炎（PN）と診断した．入院後，左尺骨神経領域にも新たに知覚異常が出現しており，進行性の神経症状に対して寛解導入療法としてステロイドパルス療法とシクロフォスファミド間欠静注療法（IVCY）を開始した．治療開始後，皮疹およびNSTでの振幅低下において改善傾向を認めている．全身性血管炎の治療においてはステロイドとIVCYの併用による有効性が大規模臨床試験において確認されている．一方，中枢神経症状やその他の重要臓器病変を伴わず，末梢神経症状のみに限局した非全身性血管炎においては，ステロイド単剤での治療における再燃例は少なくない．進行性の神経症状を呈する血管炎に対しては，発症早期からの積極的な治療介入を行うことが神経学的予後を改善する上で重要であると考える．
, 日本臨床免疫学会, 日本語

【肺高血圧症最新薬物治療の実際-膠原病・肺疾患合併編-】 症例から学ぶ 膠原病性肺高血圧症の難治症例に挑む ボセンタン、タダラフィル、免疫抑制療法が奏功した強皮症合併肺動脈性肺高血圧症、腎クリーゼの1例　　　　　　　　　　　　　　　
河野 通仁, Modern Physician, 32, 臨時増刊号2, 14, 16, 2012年07月
40歳代女性。レイノー現象を自覚し近医を受診、混合性結合組織病と診断され、ベラプロスト(120μg/日)の投与が開始されたが、2年目には両前腕の皮膚硬化が進行して強皮症への移行と考えられた。対処としてプレドニゾロン(PSL、40mg/日)の投与が行われ、また高血圧症の合併もみられたことから、アムロジピン+エナラプリルの併用も行われた。しかし、労作時呼吸困難ほか腎機能障害が出現したため、著者らの施設へ紹介となった。入院時、胸部X線像では左第2弓の突出がみられ、心エコーでは推定肺動脈収縮期圧が高値で、肺高血圧症が疑われた。一方、血液検査所見および右心カテーテル検査、胸部CTを行なったところ、その所見から本症例は膠原病性肺動脈性肺高血圧症(PAH)と強皮症腎クリーゼと診断された。以後、ボンセタン(125mg/日)+タダラフィル(20mg/日)で治療を開始し、PSLを漸減しつつ、維持療法としてアザチオプリン(50mg/日)+ボセンタン(125mg/日)+タダラフィル(20mg/日)が行われた。更にボンセタンを250mg/日、タダラフィルを40mg/日に増量した結果、3ヵ月後の評価ではWHO機能分類はIII度からII度となり、6分間歩行距離は増加、肺動脈圧も低下して肺血管抵抗も改善した。, (株)新興医学出版社, 日本語

EFFECTIVENESS OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR INTERSTITIAL LUNG DISEASES IN PATIENTS WITH SYSTEMIC SCLEROSIS
T. Odani, S. Yasuda, M. Kono, T. Kurita, Y. Fujieda, K. Otomo, Y. Kon, T. Horita, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 71, 241, 241, 2012年06月
英語, 研究発表ペーパー・要旨（国際会議）

THE EFFICACY OF TACROLIMUS IN PATIENTS WITH INTERSTITIAL LUNG DISEASES COMPLICATED WITH POLYMYOSITIS OR DERMATOMYOSITIS
T. Kurita, S. Yasuda, K. Oba, K. Otomo, H. Shida, T. Watanabe, Y. Kanetsuka, M. Kono, T. Odani, Y. Fujieda, Y. Kon, T. Horita, N. Sato, T. Atsumi, ANNALS OF THE RHEUMATIC DISEASES, 71, 233, 233, 2012年06月
英語, 研究発表ペーパー・要旨（国際会議）

リウマチ性疾患の肺病変(1) 膠原病性肺動脈性肺高血圧症23例の臨床像の解析　　　　　　　　　　　　　　　
河野 通仁, 加藤 将, 志田 玄貴, 渡邊 俊之, 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, 保田 晋助, 堀田 哲也, 渥美 達也, 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, 56回・21回, 307, 307, 2012年03月
(一社)日本リウマチ学会, 日本語

多発性筋炎・皮膚筋炎(2) 間質性肺炎を合併した皮膚筋炎・多発性筋炎の予後因子　　　　　　　　　　　　　　　
栗田 崇史, 保田 晋助, 大友 耕太郎, 志田 玄貴, 渡邊 俊之, 金塚 雄作, 河野 通仁, 小谷 俊雄, 藤枝 雄一郎, 加藤 将, 近 祐次郎, 堀田 哲也, 渥美 達也, 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, 56回・21回, 371, 371, 2012年03月
(一社)日本リウマチ学会, 日本語

血管炎(4) 中枢神経症状を呈した全身性血管炎15例の検討　　　　　　　　　　　　　　　
金塚 雄作, 堀田 哲也, 大友 耕太郎, 志田 玄貴, 渡邊 俊之, 河野 通仁, 栗田 崇史, 小谷 俊雄, 藤枝 雄一郎, 加藤 将, 近 祐次郎, 保田 晋助, 渥美 達也, 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, 56回・21回, 389, 389, 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

原発性抗リン脂質抗体症候群における全身性エリテマトーデス発症予測因子　　　　　　　　　　　　　　　
渡邊 俊之, 藤枝 雄一郎, 志田 玄貴, 金塚 雄作, 河野 通仁, 栗田 崇史, 小谷 俊雄, 大友 耕太郎, 加藤 将, 近 祐次郎, 保田 晋助, 堀田 哲也, 渥美 達也, 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, 56回・21回, 666, 666, 2012年03月
(一社)日本リウマチ学会, 日本語

【膠原病・リウマチ性疾患の治療の現状と展望】 免疫抑制薬・抗リウマチ薬 ミコフェノール酸モフェチル
河野 通仁, 渥美 達也, 日本内科学会雑誌, 100, 10, 2954, 2959, 2011年10月
ミコフェノール酸モフェチル（mycophenolate mofetil：MMF）は臓器移植後の拒絶反応に対し優れた治療効果を示してきた．そして近年，自己免疫疾患への治療応用が進んでいる．MMFはループス腎炎の寛解導入療法，寛解維持療法いずれにおいても複数のランダム化試験で有効性が報告されている．しかしMMFの長期的な有効性，安全性などは不明であり，今後更なる検討が必要である．
, (一社)日本内科学会, 日本語

抗リン脂質抗体症候群　　　　　　　　　　　　　　　
渥美 達也, 金塚 雄作, 河野 通仁, VTEジャーナル, 1, 1, 47, 47, 2011年09月
(株)メディカルレビュー社, 日本語

SLE 高用量ステロイド投与時に発症した精神神経症状の解析　　　　　　　　　　　　　　　
清水 裕香, 渥美 達也, 河野 通仁, 金塚 雄作, 栗田 崇史, 小谷 俊雄, 藤枝 雄一郎, 加藤 将, 大友 耕太郎, 深谷 進司, 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, 252, 252, 2011年06月
(一社)日本リウマチ学会, 日本語

ループス腎炎 ループス腎炎患者の腎予後の検討　　　　　　　　　　　　　　　
河野 通仁, 渥美 達也, 藤枝 雄一郎, 加藤 将, 清水 裕香, 金塚 雄作, 栗田 崇史, 小谷 俊雄, 大友 耕太郎, 深谷 進司, 保田 晋助, 堀田 哲也, 近藤 真, 向井 正也, 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, 55回・20回, 286, 286, 2011年06月
(一社)日本リウマチ学会, 日本語

リウマチ性疾患の肺病変 間質性肺炎を有する皮膚筋炎・多発性筋炎の予後因子の検討　　　　　　　　　　　　　　　
栗田 崇史, 保田 晋助, 大友 耕太郎, 金塚 雄作, 河野 通仁, 清水 裕香, 小谷 俊雄, 藤枝 雄一郎, 加藤 将, 堀田 哲也, 渥美 達也, 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, 55回・20回, 335, 335, 2011年06月
(一社)日本リウマチ学会, 日本語

強皮症 強皮症患者の間質性肺病変に対する自家末梢血幹細胞移植(aPBSCT)の有効性の検討　　　　　　　　　　　　　　　
小谷 俊雄, 保田 晋助, 清水 裕香, 河野 通仁, 金塚 雄作, 栗田 崇史, 藤枝 雄一郎, 加藤 将, 大友 耕太郎, 深谷 進司, 堀田 哲也, 渥美 達也, 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, 55回・20回, 404, 404, 2011年06月
(一社)日本リウマチ学会, 日本語

強皮症 強皮症の間質性肺病変に関連する因子の検討　　　　　　　　　　　　　　　
小谷 俊雄, 保田 晋助, 清水 裕香, 河野 通仁, 金塚 雄作, 栗田 崇史, 藤枝 雄一郎, 加藤 将, 大友 耕太郎, 深谷 進司, 堀田 哲也, 渥美 達也, 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, 55回・20回, 405, 405, 2011年06月
(一社)日本リウマチ学会, 日本語

血管炎 血管炎症候群に対するシクロフォスファミド間欠静注療法(IVCY)の長期有用性の検討　　　　　　　　　　　　　　　
金塚 雄作, 堀田 哲也, 大友 耕太郎, 河野 通仁, 清水 裕香, 栗田 崇史, 小谷 俊雄, 藤枝 雄一郎, 加藤 将, 深谷 進司, 保田 晋助, 渥美 達也, 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, 55回・20回, 442, 442, 2011年06月
(一社)日本リウマチ学会, 日本語

高用量ステロイド投与時に発症した精神神経症状の解析
清水裕香, 渥美達也, 河野通仁, 金塚雄作, 栗田崇史, 小谷俊雄, 藤枝雄一郎, 加藤将, 大友耕太郎, 深谷進司, 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, 55th-20th, 2011年

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

薬に強くなる 副腎皮質ホルモン製剤
河野 通仁, 渥美 達也, 看護技術, 56, 13, 1309, 1313, 2010年11月
(株)メヂカルフレンド社, 日本語

間質性肺炎を有する膠原病患者の予後因子の検討
栗田崇史, 金塚雄作, 河野通仁, 清水裕香, 小谷俊雄, 藤枝雄一郎, 大友耕太郎, 加藤将, 堀田哲也, 保田晋助, 小野寺祐也, 渥美達也, 小池隆夫, 日本臨床リウマチ学会プログラム・抄録集, 25th, 2010年

弛張熱で発症した原発性胆汁性肝硬変、自己免疫性肝炎合併シェーグレン症候群の1例
河野 通仁, 佐藤 力, 野本 博司, 谷口 聡, 田村 元男, 山根 康昭, 浄土 智, 藤咲 淳, 石津 明洋, 大塚 紀幸, 富居 一範, 北海道医学雑誌, 84, 5, 403, 404, 2009年09月
北海道医学会, 日本語

肺梗塞で再発した抗リン脂質抗体症候群合併SLEの1例　　　　　　　　　　　　　　　
野口 淳史, 河野 通仁, 野本 博司, 谷口 聡, 田村 元男, 山根 康昭, 浄土 智, 藤咲 淳, 苫小牧市立病院医誌, 20, 1, 9, 13, 2009年03月
苫小牧市立病院, 日本語

吃逆を呈した神経Behcet病の一例　　　　　　　　　　　　　　　
河野 通仁, 保前 英希, 中村 雅一, 畑 大, 帯広厚生病院医誌, 11, 70, 75, 2008年10月
帯広厚生病院, 日本語

Clinical effect of autologous hematopoietic stem cell transplantation against interstitial pneumonia in patients with systemic sclerosis
T. Bohgaki, T. Atsumi, M. Bohgaki, A. Furusaki, M. Kondo, M. Nishio, H. Kataoka, T. Horita, S. Yasuda, Y. Amasaki, T. Koike, ANNALS OF THE RHEUMATIC DISEASES, 66, 202, 202, 2007年07月
英語, 研究発表ペーパー・要旨（国際会議）

Thrombotic thrombocytopenic purpura in two patients with antiphospholipid syndrome
Y Kon, T Atsumi, M Kondo, Y Sakai, S Yasuda, Y Amasaki, T Koike, THROMBOSIS RESEARCH, 114, 5-6, 651, 651, 2004年
英語, 研究発表ペーパー・要旨（国際会議）

細胞内代謝を標的としたT細胞関連自己免疫性疾患の新規治療開発
科学研究費助成事業
2024年04月01日 - 2027年03月31日
河野 通仁
日本学術振興会, 基盤研究(C), 北海道大学, 24K11574

ミクログリアに注目した抗リン脂質抗体による中枢神経障害の病態解明
科学研究費助成事業
2023年04月01日 - 2026年03月31日
渥美 達也, 河野 通仁
膠原病を代表する全身性エリテマトーデス(SLE)やその関連疾患である抗リン脂質抗体症候群(APS)にみられる中枢神経症状は難治性で、患者の生命予後だけでなく患者の生活の質に直結する。APSは抗リン脂質抗体(aPL)と呼ばれる病原性自己抗体が産生され、再発性血栓症や習慣流産などを引き起こす自己免疫疾患である。APS患者では若年でも脳梗塞や心筋梗塞を来すことがあり、致命的になることもあり、また生活の質を著しく低下させ、周囲の介護など社会的な問題にもつながりうる。また、aPL陽性患者では、脳梗塞のみならず、てんかん、舞踏病、横断性脊髄症、多発性硬化症様病態などの特長ある神経疾患がよくみられ、aPL関連神経疾患とよばれる。APSの半数はSLEに合併し、SLEの多様な中枢神経症状の主要な病態のひとつがこのaPL関連神経疾患に属すると考えられる。研究代表者らは、SLEの神経症状の病態に中枢神経系の唯一の免疫細胞であるミクログリアの活性化が関わることを示してきた。本研究の目的は、aPLがミクログリアにどのような変化をもたらすのかを探求し、その機序ならびに新規治療標的分子を明らかにすることとした。これにより若年者に重篤な後遺症をもたらしうるAPS/SLEにおける中枢神経障害の予防と治療に貢献できる。また、ミクログリアの活性化を抑制するメカニズムに注目し、病態を解明することで、その他のミクログリアが関連する認知症、統合失調症、抑うつ症状などにも応用しうる。
日本学術振興会, 基盤研究(B), 北海道大学, 23K27633

ミクログリアに注目した抗リン脂質抗体による中枢神経障害の病態解明
科学研究費助成事業
2023年04月01日 - 2026年03月31日
渥美 達也, 河野 通仁
日本学術振興会, 基盤研究(B), 北海道大学, 23H02942

マルチオミクス解析を用いた細胞間相互作用に注目した精神神経ループスの病態解明　　　　　　　　　　　　　　　
難治性疾患実用化研究事業
2022年09月 - 2025年03月
日本医療研究開発機構(AMED), 研究代表者, 22ek0109607

ミクログリアに注目した精神神経ループスの病態解明
科学研究費助成事業 若手研究
2021年04月01日 - 2023年03月31日
河野 通仁
全身性エリテマトーデス(SLE)は若年女性に発症する自己免疫性疾患で様々な臓器病変を伴い生命予後も悪い。SLE患者の20～40％に精神神経ループス(NPSLE)が認められ、意識障害やてんかんなどを呈する。NPSLEはSLE患者の予後規定因子のひとつとされているが、病態は不明で、エビデンスのある治療戦略が立てられないのが現状である。ステロイド投与後にNPSLEを発症する例や、他の臓器病変を伴わない例も多く、NPSLEの病態にあった新規治療が求められている。これまでに我々はNPSLEモデルマウスを用いて、ミクログリアの活性化がNPSLEの行動異常に関与していることを示してきた。本研究ではNPSLEにおけるミクログリアの病態関与ならびに新規治療ターゲットを見いだすことを目的とする。
まず、健常者ならびにNPSLE患者の末梢血単核球からiPS細胞を樹立した。現在ミクログリアへの分化を進めている。またNPSLEモデルマウスであるMRL/lprマウスとそのコントロールマウスであるMRL/MpJマウスの脳からミクログリアを分離し、遺伝子発現の変化をRNAseqで網羅的に検討したところ、複数のターゲットが見いだされた。その中で現在遺伝子Yに注目し、阻害薬によるミクログリアの活性化ならびにNPSLEモデルマウスへの髄腔内持続静注による行動異常の改善の有無を検討している。現時点でYの阻害薬の髄腔内持続静注により、NPSLEモデルマウスの行動異常が改善することが示唆されるデータを得ている。今後Nを増やすとともにミクログリア活性化への影響などについても検討を進めていく。
日本学術振興会, 若手研究, 北海道大学, 21K16280

T細胞細胞内代謝に注目した全身性エリテマトーデスの病態解明　　　　　　　　　　　　　　　
免疫アレルギー疾患実用化研究事業
2020年11月 - 2023年03月
日本医療研究開発機構(AMED), 北海道大学, 研究代表者, 21ek0410078

精神神経ループス発症の分子機序と新規治療の開発：ミクログリアの細胞型分化機構
科学研究費助成事業 若手研究
2019年04月01日 - 2021年03月31日
河野 通仁
全身性エリテマトーデス(SLE)は自己免疫性疾患のひとつで若年女性に多く発症し、神経、腎臓、皮膚など様々な臓器病変を伴い生命予後にもかかわる。それらの中でも精神神経ループス(NPSLE)は最も重症な臓器病変のひとつである。本研究では脳細胞のうちミクログリアに注目して研究を行った。
ループスモデルマウスではコントロールマウスと比較し、ミクログリアの活性化が起きていた。さらにRNAシークエンスを行ったところ、複数のpathway、遺伝子で有意差を認めた。これらによりNPSLEにおける新規治療ターゲットが明らかとなった。
日本学術振興会, 若手研究, 北海道大学, 19K17900