Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG
Masahiro Ueki, Shinsuke Hirabayashi, Yoshitaka Honda, Shunichiro Takezaki, Hiroki Ohata, Shimaa Said Mohamed Ali Abdrabou, Saori Sawai, Yukayo Terashita, Yuko Cho, Hideki Muramatsu, Kazushi Izawa, Takahiro Yasumi, Yoshiyuki Takahashi, Masafumi Yamada, Atsushi Manabe
Immunological Medicine, 2024年11月
研究論文（学術雑誌）

A de novo dominant-negative variant is associated with OTULIN-related autoinflammatory syndrome
Yukiko Takeda, Masahiro Ueki, Junpei Matsuhiro, Erik Walinda, Takayuki Tanaka, Masafumi Yamada, Hiroaki Fujita, Shunichiro Takezaki, Ichiro Kobayashi, Sakura Tamaki, Sanae Nagata, Noriko Miyake, Naomichi Matsumoto, Mitsujiro Osawa, Takahiro Yasumi, Toshio Heike, Fumiaki Ohtake, Megumu K. Saito, Junya Toguchida, Junko Takita, Tadashi Ariga, Kazuhiro Iwai
Journal of Experimental Medicine, 2024年06月03日
研究論文（学術雑誌）

Chronic Ileum Obstruction, Granulation, and Ulceration With IgG4-Positive Plasma Cell Infiltration in a Six-Year-Old Girl With 21trisomy
Ueki Masahiro
2024年
研究論文（学術雑誌）

The clinical importance of pulmonary gene and protein expression levels in an infant with lethal ABCA3 variants
Jiro Abe, Masahiro Ueki, Ryota Honjou, Kenta Takeda, Yoshitaka Seto, Yuichi Nakamura, Yuta Furuse, Koh Nakata, Kazutoshi Cho
Pediatric Pulmonology, 58, 10, 2956, 2959, Wiley, 2023年07月21日
研究論文（学術雑誌）

A case of infantile Barth syndrome with severe heart failure: Importance of splicing variants in the TAZ gene.
Atsuhito Takeda, Masahiro Ueki, Jiro Abe, Kazuhiro Maeta, Tomoko Horiguchi, Hirokuni Yamazawa, Gaku Izumi, Ayako Chida-Nagai, Daisuke Sasaki, Takao Tsujioka, Itsumi Sato, Masahiro Shiraishi, Masafumi Matsuo
Molecular genetics & genomic medicine, 11, 7, e2190, 2023年04月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Barth syndrome (BTHS) is an X-linked disorder characterized by cardiomyopathy, skeletal myopathy, and 3-methylglutaconic aciduria. The causative pathogenic variants for BTHS are in TAZ, which encodes a putative acyltransferase named tafazzin and is involved in the remodeling of cardiolipin in the inner mitochondrial membranes. Pathogenic variants in TAZ result in mitochondrial structural and functional abnormalities. We report a case of infantile BTHS with severe heart failure, left ventricular noncompaction, and lactic acidosis, having a missense c.640C>T (p.His214Tyr) variant in TAZ, which is considered a pathogenic variant based on the previously reported amino acid substitution at the same site (c.641A>G, p.His214Arg). However, in this previously reported case, heart function was compensated and not entirely similar to the present case. Silico prediction analysis suggested that c.640C>T could alter the TAZ messenger RNA (mRNA) splicing process. TAZ mRNAs in isolated peripheral mononuclear cells from the patient and in vitro splicing analysis using minigenes of TAZ found an 8 bp deletion at the 3' end of exon 8, which resulted in the formation of a termination codon in the coding region of exon 9 (H214Nfs*3). These findings suggest that splicing abnormalities should always be considered in BTHS.

The heterozygous NUDT15 variant is not associated with the severity of 6-mercaptopurine-related side effects in early intensification therapy for childhood acute lymphoblastic leukemia
Jimei Zhao, Masahiro Ueki, Saori Sawai, Minako Sugiyama, Yukayo Terashita, Shinsuke Hirabayashi, Yuko Cho, Ryoji Kobayashi, Yoichi Tanaka, Atsushi Manabe
EJC Paediatric Oncology, 1, 100006, 100006, Elsevier BV, 2023年
研究論文（学術雑誌）

Rheumatologic manifestations with elevated levels of IL-6, IL-17A, and IL-23 in a patient with scurvy
Masahiro Ueki, Keita Sakamoto, Noriko Nishioka, Hiroki Ohata, Takiko Nobuta, Shunichiro Takezaki, Atsushi Manabe, Masafumi Yamada
Modern Rheumatology Case Reports, Oxford University Press (OUP), 2022年08月09日
研究論文（学術雑誌）, ABSTRACT

Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4 months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.

Development of Graves’ disease during drug-free remission of juvenile dermatomyositis
Ichiro Kobayashi, Masaki Shimomura, Masahiro Ueki, Shunichiro Takezaki, Yuka Okura, Mitsuru Nawate, Masafumi Yamada, Yutaka Takahashi, Tadashi Ariga
Modern Rheumatology Case Reports, 6, 1, 55, 58, Oxford University Press (OUP), 2022年01月07日
研究論文（学術雑誌）, ABSTRACT

We report a Japanese boy with Graves’ disease (GD) which developed during drug-free remission of juvenile dermatomyositis (JDM). He had been diagnosed with JDM at the age of 6 years by typical skin rashes, muscle weakness, elevated serum transaminase levels, and typical findings of both magnetic resonance imaging and muscle biopsy. Although anti-melanoma differentiation antigen 5 autoantibody was positive, there was no complication of interstitial lung disease. He showed good response to methylprednisolone pulse therapy followed by oral prednisolone in combination with weekly methotrexate (MTX) and achieved drug-free remission after 3.5 years of treatment. Nevertheless, serum levels of soluble interleukin-2 receptor (sIL-2R) gradually elevated to 3185 U/ml despite no signs of relapse or malignancy. Hyperactivity and attention deficit was also noted. One year and 3 months after the cessation of MTX, he presented with abdominal pain, tachycardia, and apparent goitre. Laboratory tests showed elevated free triiodothyronine, undetectable thyroid stimulating hormone (TSH), and positive anti-TSH receptor antibodies. 99mTc scintigraphy showed high levels of thyroid uptake. He was diagnosed with GD and treated with 15 mg/day of thiamazole. Although transient drug eruption was observed, his thyroid functions are currently well-controlled on 5 mg/day of thiamazole. In conclusion, to our knowledge, this is the first report in English literature describing complication of GD with JDM. Unexpected elevation of sIL-2R could be a clue to the diagnosis of GD during the follow-up of JDM.

Coexistence of acute poststreptococcal glomerulonephritis and acute rheumatic fever in a Japanese girl with primary Sjögren's syndrome.
Ichiro Kobayashi, Shunichiro Takezaki, Yusuke Tozawa, Masahiro Ueki, Asako Hayashi, Takeshi Yamazaki, Yasuyuki Sato, Takayuki Okamoto, Masafumi Yamada, Tadashi Ariga
Modern rheumatology case reports, 4, 2, 262, 266, 2020年07月, ［国際誌］
英語, 研究論文（学術雑誌）, Although acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever (ARF) are well-known complications of group A streptococcus infection, concomitant occurrence of both diseases is rare. We report an 11-year-old Japanese girl with primary Sjögren's syndrome complicated by acute renal failure about 2 weeks after the onset of pharyngitis. Although histopathological findings of the kidney were not confirmative, APSGN was suggested by the spontaneous recovery of her renal function, typical latent period with high levels of antistreptolysin O and low serum levels of C3 but not of C4. In addition, cardiac hypomotility and regurgitation of the 4 valves progressed in the convalescent phase of APSGN, which was accompanied by elevation of serum C-reactive protein and plasma brain natriuretic peptide (BNP) levels. Myocarditis was suggested by delayed gadolinium-enhancement of cardiac walls on cardiac magnetic resonance imaging. She was diagnosed with APSGN and ARF and was treated with a combination of short course prednisolone and prophylactic penicillin G. There is no relapse of renal or cardiac symptoms during 6 years follow-up. Unexpected elevation of plasma BNP in a convalescent stage of APSGN suggests the development of ARF. Underlying Sjögren's syndrome (SS) may modify the histopathological findings and make it difficult to differentiate APSGN from CTD-associated nephritis such as lupus nephritis (LN) even by renal biopsy.

多彩な自己炎症性疾患を紐解く Linear ubiquitin assembly complexとOTULINによる炎症と細胞死の制御 OTULIN-related autoinflammatory syndrome患者の解析を通して　　　　　　　　　　　　　　　
植木 将弘, 松廣 淳平, 竹崎 俊一郎, 藤田 宏明, 三宅 紀子, 戸澤 雄介, 山田 雅文, 小林 一郎, 松本 直通, 有賀 正, 岩井 一宏, 真部 淳
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 29回, 52, 52, (一社)日本小児リウマチ学会, 2019年10月, ［査読有り］
日本語

Myositis-specific autoantibodies in Japanese patients with juvenile idiopathic inflammatory myopathies.
Masahiro Ueki, Ichiro Kobayashi, Shunichiro Takezaki, Yusuke Tozawa, Yuka Okura, Masafumi Yamada, Masataka Kuwana, Tadashi Ariga
Modern rheumatology, 29, 2, 351, 356, 2019年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The aim of our study is to clarify the association of myositis-specific autoantibodies (MSAs) with clinical and laboratory features in Japanese patients with juvenile idiopathic inflammatory myopathies (JIIMs). METHODS: We retrospectively analyzed the frequency of MSAs and their association with clinical or laboratory findings in 25 Japanese patients with JIIMs in Hokkaido district. RESULTS: Eighteen of the 25 patients (72%) were positive for MSAs; seven with anti-melanoma differentiation associated gene (MDA) 5 (28%), five with anti-transcriptional intermediary factor (TIF)-1γ (20%), four with anti-MJ/nuclear matrix protein (NXP)-2 (16%), two with anti-Jo-1 (8%), one with anti- HMG-CoA reductase, one with anti-signal recognition peptide (SRP) antibodies (4% each), including co-existence and transition of MSAs in one patient each. Anti-MDA5 antibodies were related to interstitial lung disease (ILD) and arthritis but not to amyopathic juvenile dermatomyositis. Drug-free remission was achieved, once ILD was overcome in this group. Anti-TIF-1γ antibodies were associated with typical rashes and mild myositis. Anti-MJ/NXP2 and anti-SRP antibodies were associated with severe muscle weakness. No patient was complicated with malignancy. CONCLUSION: Anti-MDA5 antibodies are prevalent and closely associated with ILD in our series compared with other countries. There was no apparent difference in clinical features associated with other MSAs among races.

Evaluation of systemic activity of pediatric primary Sjögren's syndrome by EULAR Sjögren's syndrome disease activity index (ESSDAI).
Ichiro Kobayashi, Yuka Okura, Masahiro Ueki, Yusuke Tozawa, Shunichiro Takezaki, Masafumi Yamada, Tadashi Ariga
Modern rheumatology, 29, 1, 130, 133, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The purpose of this study is to evaluate systemic disease activity of pediatric Sjögren's syndrome (SS) using European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). METHODS: We retrospectively reviewed medical records of patients with SS who have been diagnosed according to 1999 Japanese diagnostic criteria for SS before 16 years old at KKR Sapporo Medical Center, Hokkaido University Hospital, and affiliated hospitals. We analyzed clinical and laboratory data and calculated ESSDAI at both diagnosis and peak activity. RESULTS: Twenty-five patients (2 boys and 23 girls) were enrolled. Only 4 patients had sicca symptoms at diagnosis. Mean ESSDAI scores at diagnosis and peak activity were 12.68 (2-31) and 15.08 (2-38), respectively. Only 3 patients were inactive (ESSDAI score <5) at diagnosis. Frequently involved domains at diagnosis were the biological (96%) followed by the constitutional (68%), glandular (44%), articular (44%), cutaneous domains (28%), renal (16%), and central nervous system (12%). At peak activity, biological domain (96%) was followed by the constitutional (72%), glandular (60%), articular (44%), cutaneous (28%), central nervous system (20%), and renal domains (16%). CONCLUSION: Pediatric SS is suspected from active systemic manifestations. The items of ESSDAI are useful clues to the diagnosis of pediatric SS.

遷延する発熱と骨・関節痛で発症し慢性非細菌性骨髄炎(CNBO)と診断した1例　　　　　　　　　　　　　　　
瀬戸 康貴, 木村 修平, 植木 将弘, 内田 雅也, 上野 倫彦, 竹崎 俊一郎, 戸澤 雄介, 山田 雅文
日本小児科学会雑誌, 122, 11, 1745, 1745, (公社)日本小児科学会, 2018年11月, ［査読有り］
日本語

Hematopoietic stem cell transplantation for pulmonary alveolar proteinosis associated with primary immunodeficiency disease.
Mari Tanaka-Kubota, Koji Shinozaki, Satoshi Miyamoto, Masakatsu Yanagimachi, Tsubasa Okano, Noriko Mitsuiki, Masahiro Ueki, Masafumi Yamada, Kohsuke Imai, Masatoshi Takagi, Kazunaga Agematsu, Hirokazu Kanegane, Tomohiro Morio
International journal of hematology, 107, 5, 610, 614, 2018年05月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Pulmonary alveolar proteinosis (PAP) is a rare disorder that is characterized by the excessive accumulation of surfactant-like materials in the alveoli, leading to hypoxemic respiratory failure. We describe two Japanese infants with PAP associated with hypogammaglobulinemia and monocytopenia. These patients may have underlying primary immunodeficiency (PID) and were successfully treated with allogeneic hematopoietic stem cell transplantation (HSCT). This report indicates that allogeneic HSCT may provide a curative treatment for PAP associated with PID.

Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia.
Kazutoshi Cho, Masafumi Yamada, Kazunaga Agematsu, Hirokazu Kanegane, Noriko Miyake, Masahiro Ueki, Takuma Akimoto, Norimoto Kobayashi, Satoru Ikemoto, Mishie Tanino, Atsushi Fujita, Itaru Hayasaka, Satoshi Miyamoto, Mari Tanaka-Kubota, Koh Nakata, Masaaki Shiina, Kazuhiro Ogata, Hisanori Minakami, Naomichi Matsumoto, Tadashi Ariga
American journal of human genetics, 102, 3, 480, 486, 2018年03月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2,'5'-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother's peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs.

Progression of palindromic rheumatism to juvenile idiopathic arthritis in a Japanese girl carrying heterozygous L110P-E148Q substitutions of MEFV gene.
Ichiro Kobayashi, Yasuhiro Yamazaki, Yusuke Tozawa, Masahiro Ueki, Shunichiro Takezaki, Masafumi Yamada, Tadashi Ariga
Modern rheumatology, 28, 2, 365, 368, Informa Healthcare, 2018年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Palindromic rheumatism (PR), a rare disease in children, is characterized by recurrent arthritis or periarthritis and asymptomatic interval. We report evolution of PR to juvenile idiopathic arthritis in a Japanese girl with heterozygous complex L110P-E148Q allele of MEFV gene. Poor response to colchicine alone suggests that the MEFV substitution could increase the susceptibility to arthritis rather than caused arthritis associated with atypical Familial Mediterranean Fever. Weekly methotrexate is a choice for such cases.

Relapsing Polychondritis With Increased Bone Marrow Signal on Magnetic Resonance Imaging in a 13-Year-Old Girl.
Kanako Nakayama, Sayaka Yamamoto, Kimiaki Uetake, Masafumi Yamada, Yusuke Tozawa, Masahiro Ueki, Shunichiro Takezaki, Hiroki Nishimura, Yuji Nakamaru, Tomoko Mitsuhashi, Noriko Oyama-Manabe, Keita Sakamoto, Ryuta Arai, Tadashi Ariga
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 24, 1, 52, 54, 2018年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Difficulty in the diagnosis of bone and joint pain associated with pediatric acute leukemia; comparison with juvenile idiopathic arthritis.
Takao Tsujioka, Minako Sugiyama, Masahiro Ueki, Yusuke Tozawa, Shunichiro Takezaki, Junjiro Ohshima, Yuko Cho, Masafumi Yamada, Akihiro Iguchi, Ichiro Kobayashi, Tadashi Ariga
Modern rheumatology, 28, 1, 108, 113, 2018年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Acute leukemia often causes osteoarthralgia. The aim of this study is characterization of leukemia-associated osteoarthralgia in comparison with juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed clinical records of 31 patients with acute leukemia and 13 patients with articular JIA diagnosed between January 2008 and March 2013. Clinical and laboratory findings at the initial examination were compared among the three groups; 10 leukemia with and 21 leukemia without osteoarthralgia and 13 JIA groups. RESULTS: Eleven of the 31 leukemic patients (35%) had osteoarthralgia before the diagnosis of leukemia. Peripheral leukemic cells were initially absent in 10 of the 31 leukemia patients including three with osteoarthralgia. Platelet counts over 300 × 109/L were common in JIA, but not in osteoarthralgia group. Mean serum lactate dehydrogenase levels were higher in both of the leukemia groups than JIA group but often within normal or near-normal levels in the leukemia groups. Magnetic resonance imaging was examined in three leukemic patients and demonstrated osteomyelitis-like bone marrow edema in two and periarticular infiltration similar to synovitis in one patient. Three leukemic patients with osteoarthralgia showed partial and transient responses to antibiotic therapy. CONCLUSIONS: Leukemia-associated osteoarthralgia is often indistinguishable from rheumatic diseases by imaging and laboratory findings and should be confirmed by bone marrow examination.

Successful bone marrow transplantation in two sisters with activated phosphoinositide 3-kinase δ syndrome 2
M. Sugiyama, A. Iguchi, M. Yamada, Y. Terashita, J. Ohshima, Y. Cho, N. Miyake, N. Matsumoto, M. Ueki, Y. Yamazaki, S. Takezaki, I. Kobayashi, T. Ariga
Bone Marrow Transplantation, 52, 12, 1678, 1680, Nature Publishing Group, 2017年12月01日, ［査読有り］
英語, 研究論文（学術雑誌）

血球貪食性リンパ組織球症と治療抵抗性炎症性腸疾患を合併したXIAP欠損症の1例　　　　　　　　　　　　　　　
戸澤 雄介, 山田 雅文, Abdrabou Shimaa, 植木 将弘, 竹崎 俊一郎, 有賀 正, 蘆田 知史
日本小児科学会雑誌, 121, 11, 1887, 1887, (公社)日本小児科学会, 2017年11月, ［査読有り］
日本語

小児原発性シェーグレン症候群25例における疾患活動性(ESSDAI)の検討　　　　　　　　　　　　　　　
小林 一郎, 大倉 有加, 瀬川 佳帆子, 大島 由季代, 縄手 満, 吉岡 幹朗, 高橋 豊, 戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 山田 雅文, 有賀 正
日本小児科学会雑誌, 121, 11, 1892, 1892, (公社)日本小児科学会, 2017年11月, ［査読有り］
日本語

若年性特発性炎症性筋症における筋炎特異的自己抗体と臨床症状・治療経過・予後の関連性についての検討　　　　　　　　　　　　　　　
植木 将弘, 小林 一郎, 竹崎 俊一郎, 大倉 有加, 戸澤 雄介, 山田 雅文, 桑名 正隆, 有賀 正
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 27回, 69, 69, (一社)日本小児リウマチ学会, 2017年10月, ［査読有り］
日本語

小児の自己免疫疾患、自己炎症疾患の病態と治療 小児期発症抗SRP抗体陽性壊死性筋炎の1例
小林 一郎, 戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 渡邊 誠司, 岩淵 英人, 山田 雅文, 桑名 正隆, 有賀 正
アレルギー, 66, 4-5, 636, 636, (一社)日本アレルギー学会, 2017年05月, ［査読有り］
日本語

合成着色料(赤色102号)アレルギーが強く疑われた一例
竹崎 俊一郎, 戸澤 雄介, 吉川 佳那, 植木 将弘, 石津 桂, 山田 雅文, 有賀 正
アレルギー, 66, 4-5, 681, 681, (一社)日本アレルギー学会, 2017年05月, ［査読有り］
日本語

13歳発症の再発性多発軟骨炎　　　　　　　　　　　　　　　
西村 弘基, 戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 山田 雅文, 有賀 正, 中丸 裕爾, 三橋 智子, 中山 加奈子, 山本 さやか, 原 和也, 鎌田 晃嘉, 鈴木 雅彦, 八鍬 聡, 那須 敬, 植竹 公明
日本小児科学会雑誌, 121, 1, 119, 119, (公社)日本小児科学会, 2017年01月, ［査読有り］
日本語

A heterozygous dominant-negative mutation in the coiled-coil domain of STAT1 is the cause of autosomal-dominant Mendelian susceptibility to mycobacterial diseases.
Masahiro Ueki, Masafumi Yamada, Kenta Ito, Yusuke Tozawa, Saeko Morino, Yuho Horikoshi, Hidetoshi Takada, Shimaa Said Mohamed Ali Abdrabou, Shunichiro Takezaki, Ichiro Kobayashi, Tadashi Ariga
Clinical immunology (Orlando, Fla.), 174, 24, 31, 2017年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Heterozygous dominant-negative mutations of STAT1 are responsible for autosomal-dominant Mendelian susceptibility to mycobacterial diseases (AD-MSMD). So far, only 7 mutations have been previously described and are localized to 3 domains: the DNA-binding domain, the SH2 domain, and the tail segment. In this study, we demonstrated the first coiled-coil domain (CCD) mutation of c.749G>C, p.G250A (G250A) in STAT1 as a genetic cause of AD-MSMD in a patient with mycobacterial multiple osteomyelitis. This de novo heterozygous mutation was shown to have a dominant-negative effect on the gamma-activated sequence (GAS) transcriptional activity following IFN-γ stimulation, which could be attributable to the abolished phosphorylation of STAT1 from the wild-type (WT) allele. The three-dimensional structure of STAT1 revealed the G250 residue was located distant from a cluster of residues affected by gain-of-function mutations responsible for chronic mucocutaneous candidiasis.

無菌性髄膜炎を合併したシェーグレン症候群5例の検討　　　　　　　　　　　　　　　
大倉 有加, 小林 一郎, 高橋 豊, 戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 山田 雅文, 有賀 正
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 26回, 85, 85, (一社)日本小児リウマチ学会, 2016年10月, ［査読有り］
日本語

骨関節痛を伴った急性白血病と若年性特発性関節炎の比較検討　　　　　　　　　　　　　　　
辻岡 孝郎, 小林 一郎, 植木 将弘, 戸澤 雄介, 杉山 未奈子, 竹崎 俊一郎, 大島 淳二郎, 井口 晶裕, 長 祐子, 山田 雅文, 有賀 正
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 26回, 95, 95, (一社)日本小児リウマチ学会, 2016年10月, ［査読有り］
日本語

MRIで骨に異常信号を認めた再発性多発軟骨炎の小児例　　　　　　　　　　　　　　　
戸澤 雄介, 山田 雅文, 植木 将弘, 竹崎 俊一郎, 中丸 裕爾, 中山 加奈子, 山本 さやか, 原 和也, 鎌田 晃嘉, 鈴木 雅彦, 八鍬 聡, 那須 敬, 植竹 公明, 三橋 智子, 有賀 正
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 26回, 124, 124, (一社)日本小児リウマチ学会, 2016年10月, ［査読有り］
日本語

EBウイルス感染後に関節炎が消退した多関節型若年性特発性関節炎の1例
植木 将弘, 山崎 康博, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正
臨床小児医学, 63, 1-6, 47, 47, (財)小児愛育協会, 2015年12月, ［査読有り］
日本語

関節炎を契機に診断された炎症性腸疾患(IBD)の2例
植木 将弘, 戸澤 雄介, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正
臨床小児医学, 63, 1-6, 49, 49, (財)小児愛育協会, 2015年12月, ［査読有り］
日本語

小児期発症虚血性ループス腸炎の2例　　　　　　　　　　　　　　　
河野 修, 加藤 晶, 佐藤 紀夫, 藤本 隆憲, 安藤 明子, 菅沼 隆, 佐藤 智信, 三河 誠, 戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 25回, 132, 132, (一社)日本小児リウマチ学会, 2015年10月, ［査読有り］
日本語

全身浮腫で発症したSLE・シェーグレン症候群(SS)の小児例
植木 将弘, 戸澤 雄介, 竹崎 俊一郎, 小西 祥平, 山田 雅文, 小林 一郎, 有賀 正
日本臨床免疫学会会誌, 38, 4, 373, 373, 日本臨床免疫学会, 2015年09月, ［査読有り］
日本語

アトバコンが有効であった小児ニューモシスチス肺炎の2例　　　　　　　　　　　　　　　
植木 将弘, 山崎 康博, 竹崎 俊一郎, 大倉 有加, 山田 雅文, 小林 一郎, 有賀 正
小児感染免疫, 27, 1, 47, 48, 日本小児感染症学会, 2015年04月, ［査読有り］
日本語

膠原病・自己免疫疾患 若年性皮膚筋炎(JDM)における抗ARS抗体測定の有用性の検討
竹崎 俊一郎, 戸澤 雄介, 植木 将弘, 山田 雅文, 小林 一郎, 有賀 正
アレルギー, 64, 3-4, 481, 481, (一社)日本アレルギー学会, 2015年04月, ［査読有り］
日本語

関節痛を主症状とした若年性皮膚筋炎(JDM)の2例　　　　　　　　　　　　　　　
植木 将弘, 戸澤 雄介, 山崎 康博, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正
日本小児科学会雑誌, 119, 2, 508, 508, (公社)日本小児科学会, 2015年02月, ［査読有り］
日本語

Disease specificity of anti-tryptophan hydroxylase-1 and anti-AIE-75 autoantibodies in APECED and IPEX syndrome
Natsuko Chida, Ichiro Kobayashi, Shunichiro Takezaki, Masahiro Ueki, Yasuhiro Yamazaki, Silvia Garelli, Riccardo Scarpa, Reiko Horikawa, Masafumi Yamada, Corrado Betterle, Luigi D. Notarangelo, Yasutaka Yawaka, Tadashi Ariga
CLINICAL IMMUNOLOGY, 156, 1, 36, 42, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Autoantibodies to autoimmune enteropathy-related 75 kDa antigen (AIE-75) and villin are disease markers of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome which is characterized by a peripheral tolerance defect. On the other hand, anti-tryptophan hydroxylase-1 (TPH-1) antibodies are detected in autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED), a central tolerance defect, especially when complicated with gastrointestinal dysfunction. However, to date, anti-AIE-75 and anti-villin antibodies or anti-TPH-1 antibodies have not been tested in APECED or IPEX syndrome, respectively. In the present study, we confirmed the disease specificity of both anti-AIE-75 and anti-TPH-1, although anti-villin antibodies were detected in some patients with APECED. Our observation suggests that immunotolerance to AIE-75 depends on the peripheral mechanism, whereas the tolerance to TPH-1 depends on the central mechanisms. (C) 2014 Elsevier Inc. All rights reserved.

Two novel gain-of-function mutations of STAT1 responsible for chronic mucocutaneous candidiasis disease: impaired production of IL-17A and IL-22, and the presence of anti-IL-17F autoantibody.
Yasuhiro Yamazaki, Masafumi Yamada, Toshinao Kawai, Tomohiro Morio, Masafumi Onodera, Masahiro Ueki, Nobuyuki Watanabe, Hidetoshi Takada, Shunichiro Takezaki, Natsuko Chida, Ichiro Kobayashi, Tadashi Ariga
Journal of immunology (Baltimore, Md. : 1950), 193, 10, 4880, 7, The American Association of Immunologists, 2014年11月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Heterozygous gain-of-function (GOF) mutations of STAT1 are responsible for chronic mucocutaneous candidiasis disease (CMCD), one of the primary immunodeficiency diseases characterized by susceptibility to mucocutaneous Candida infection. To date, 30 aa changes have been reported: 21 in the coiled-coil domain and 9 in the DNA-binding domain. In this study, we report two novel STAT1 GOF mutations of p.K278E in coiled-coil domain and p.G384D in DNA-binding domain in Japanese CMCD patients. Ectopic expression of these STAT1 mutants in HeLa cells was associated with increased phosphorylation of the mutant and the endogenous wild-type STAT1 due to impaired dephosphorylation, indicating heterodimers of the wild-type and mutant STAT1 cause impaired dephosphorylation, as did homodimers of the mutants. Because IL-17A production was not significantly reduced at least in one of the patients following PMA plus ionomycin stimulation, we further studied Th17-associated cytokines IL-17A, IL-17F, and IL-22 in response to more physiologically relevant stimulations. IL-17A and IL-22 production from PBMCs and CD4(+) cells was significantly reduced in four patients with STAT1 GOF mutations, including the previously reported R274Q in response to anti-CD3 plus anti-CD28 Abs or Candida stimulations. In contrast, IL-17F production was comparable to healthy controls in response to anti-CD3 plus anti-CD28 Abs stimulation. These results indicate impaired production of IL-17A and IL-22 rather than IL-17F was associated with the development of CMCD in these patients. Additionally, only the anti-IL-17F autoantibody was detected in sera from 11 of 17 patients with STAT1 GOF mutations, which may be useful as a marker for this disease.

APECEDおよびIPEX症候群における抗トリプトファン水酸化酵素-1抗体および抗AIE-75抗体の疾患特異性の検討
千田 奈津子, 小林 一郎, 植木 将弘, 山崎 康博, 竹崎 俊一郎, 堀川 玲子, Notarangelo Luigi D., Corrado Betterle, 山田 雅文, 有賀 正
日本臨床免疫学会会誌, 37, 4, 335, 335, 日本臨床免疫学会, 2014年08月, ［査読有り］
日本語

肝膿瘍を発症した自己免疫性好中球減少症の1例　　　　　　　　　　　　　　　
竹崎 俊一郎, 植木 将弘, 戸澤 雄介, 山崎 康博, 藤田 祥二, 阿部 修司, 井口 晶裕, 山田 雅文, 小林 一郎, 中村 和洋, 有賀 正
日本小児科学会雑誌, 118, 3, 579, 580, (公社)日本小児科学会, 2014年03月, ［査読有り］
日本語

骨関節痛で発症した急性白血病の2例　　　　　　　　　　　　　　　
辻岡 孝郎, 植木 将弘, 寺下 友佳代, 杉山 美奈子, 山崎 康博, 竹崎 俊一郎, 大島 淳二郎, 佐藤 智信, 長 祐子, 井口 晶裕, 山田 雅文, 小林 一郎, 有賀 正
日本小児科学会雑誌, 118, 3, 580, 580, (公社)日本小児科学会, 2014年03月, ［査読有り］
日本語

筋力低下を伴わず一過性筋原性酵素上昇とMRI異常を認めた若年性皮膚筋炎の2症例
植木 将弘, 山崎 康博, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正
アレルギー, 62, 9-10, 1348, 1348, (一社)日本アレルギー学会, 2013年10月, ［査読有り］
日本語

筋力低下を伴わず、一過性の筋原性酵素上昇とMRI異常を認めた若年性皮膚筋炎の2症例　　　　　　　　　　　　　　　
植木 将弘, 山崎 康博, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正
日本小児リウマチ学会総会・学術集会プログラム・抄録集, 23回, 105, 105, (一社)日本小児リウマチ学会, 2013年10月, ［査読有り］
日本語

A case of recurrent rhabdomyolysis associated with childhood Sjögren’s syndrome
Shuntaro Morikawa, Ichiro Kobayashi, Yutaka Uzuki, Masahiro Ueki, Tetsuo Hattori, Hayato Aoyagi
OJPed, 03, 03, 276, 278, Scientific Research Publishing, Inc,, 2013年, ［査読有り］
研究論文（学術雑誌）

乳児へのボリコナゾール投与中に、代謝機能の発達によると考えられる著しい血中濃度低下が認められた1例
山口 敦史, 田澤 佑基, 武隈 洋, 植木 将弘, 山田 雅文, 真鍋 淳, 菅原 満, TDM研究, 39, 2, 136, 136, 2022年05月
(一社)日本TDM学会, 日本語

【自己炎症性疾患-最新の基礎・臨床知見-】狭義の自己炎症性疾患 LUBAC関連疾患(HOIL-1欠損症、HOIP欠損症、OTULIN欠損症)
植木 将弘, 山田 雅文, 日本臨床, 76, 10, 1837, 1843, 2018年10月
(株)日本臨床社, 日本語

Tacrolimus in combination with methotrexate and corticosteroid for the treatment of child-onset anti-signal recognition particle antibody-positive necrotizing myopathy
I. Kobayashi, Y. Tozawa, M. Ueki, S. Takezaki, S. Watanabe, H. Iwafuchi, M. Yamada, M. Kuwana, T. Ariga, Scandinavian Journal of Rheumatology, 46, 5, 409, 410, 2017年09月03日
Taylor and Francis Ltd, 英語, 速報，短報，研究ノート等（学術雑誌）

Successful allogeneic unrelated bone marrow transplantation in a female patient with a heterozygous splice-site mutation in PIK3R1
M. Sugiyama, Y. Terashita, J. Ohshima, Y. Cho, A. Iguchi, M. Ueki, Y. Tozawa, S. Takezaki, M. Yamada, I. Kobayashi, T. Ariga, BONE MARROW TRANSPLANTATION, 51, S460, S461, 2016年03月
NATURE PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

成長障害を生じた限局性強皮症の2例　　　　　　　　　　　　　　　
戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 山田 雅文, 小林 一郎, 有賀 正, 畑中 佳奈子, 日本小児リウマチ学会総会・学術集会プログラム・抄録集, 25回, 144, 144, 2015年10月
(一社)日本小児リウマチ学会, 日本語

溶連菌感染後糸球体腎炎とリウマチ熱の同時発症が考えられたシェーグレン症候群の一例　　　　　　　　　　　　　　　
竹崎 俊一郎, 植木 将弘, 林 麻子, 山崎 健史, 山崎 康博, 佐藤 泰征, 岡本 孝之, 藤田 裕美, 山田 雅文, 小林 一郎, 有賀 正, 日本小児リウマチ学会総会・学術集会プログラム・抄録集, 23回, 112, 112, 2013年10月
(一社)日本小児リウマチ学会, 日本語

当院で経験したSchinzel-Giedion症候群の1例　　　　　　　　　　　　　　　
米丸 希, 山上 雄司, 鈴木 雅彦, 脇口 定衛, 奥原 宏治, 飯塚 進, 植木 将弘, 植竹 弘明, 小林 良二, 黒澤 健司, 外木 秀文, 日本小児科学会雑誌, 116, 12, 1954, 1954, 2012年12月
(公社)日本小児科学会, 日本語

脳室周囲白質軟化症(Periventricular leukomalacia:PVL)を認めた先天性筋強直性ジストロフィーの早産児例　　　　　　　　　　　　　　　
森岡 圭太, 上田 泰弘, 森川 俊太郎, 小杉山 清隆, 山崎 健史, 植木 将弘, 日本小児科学会雑誌, 115, 11, 1814, 1814, 2011年11月
(公社)日本小児科学会, 日本語

神経性食思不振症にRefeeding syndromeを合併した一例　　　　　　　　　　　　　　　
泉 岳, 植木 将弘, 小西 貴幸, 斎田 吉伯, 三河 誠, 小林 一郎, 日本小児栄養消化器肝臓学会雑誌, 23, Suppl., 98, 98, 2009年09月
日本小児栄養消化器肝臓学会, 日本語