Faculty Profiles - katsuyama eri

Papers - katsuyama eri

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Dyspnea with Hemidiaphragm Elevation in a Patient with Giant Cell Arteritis: A Case Report

Yosuke Asano, Yoshinori Matsumoto, Natsuki Kubota, Yuya Terajima, Kazuya Matsumoto, Kenta Shidahara, Kei Hirose, Takato Nakadoi, Shoichi Nawachi, Yu Katayama, Yoshia Miyawaki, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Ken-Ei Sada, Jun Wada

Internal Medicine 2025

Pericardial artery lymphoma in a patient with dermatomyositis: A case report. International journal

Kei Hirose, Takayuki Katsuyama, Natsuki Kubota, Yuya Terajima, Kazuya Matsumoto, Kenta Shidahara, Takato Nakadoi, Shoichi Nawachi, Yu Katayama, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki-Takano, Yoshinori Matsumoto, Noboru Asada, Ken-Ei Sada, Jun Wada

Modern rheumatology case reports 2024.11

Language：English Publishing type：Research paper (scientific journal)

A woman in her 60s presented with erythema on both elbows, dyspnea on exertion, discomfort, and swelling of the left upper extremity, followed by swelling and myalgia of the right upper and lower extremities. She was diagnosed with anti-TIF1γ antibody-positive dermatomyositis with interstitial pneumonia. The initial screening tests for malignant diseases including contrast-enhanced CT, upper and lower endoscopy, and gynecological examination did not reveal any obvious abnormalities. The patient experienced two recurrent episodes of muscle weakness and dysphagia during treatment with intravenous glucocorticoids and cyclophosphamide. Five months after diagnosis, a bone marrow biopsy and positron emission tomography- computed tomography (PET-CT) scan revealed a coronary malignant lymphoma with suspected systemic metastasis. Although chemotherapy was initiated, the patient ultimately succumbed to alveolar hemorrhage. Coronary lymphoma is very rare and there has been no report of a cases associated with myositis. PET-CT may be useful for searching malignancy in anti-TIF1γ antibody-positive dermatomyositis cases of recurrent relapse.

DOI： 10.1093/mrcr/rxae065

Association between discontinuity of care and patient trust in the usual rheumatologist among patients with systemic lupus erythematosus: a cross-sectional study

Yu Katayama, Yoshia Miyawaki, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nao Oguro, Nobuyuki Yajima, Yuichi Ishikawa, Natsuki Sakurai, Chiharu Hidekawa, Ryusuke Yoshimi, Shigeru Ohno, Takanori Ichikawa, Dai Kishida, Yasuhiro Shimojima, Ken-ei Sada, Jun Wada, David H. Thom, Noriaki Kurita

Arthritis Research & Therapy 26 ( 1 ) 2024.11

CD38 in SLE CD4 T cells promotes Ca2+ flux and suppresses interleukin-2 production by enhancing the expression of GM2 on the surface membrane

Eri Katsuyama, Morgane Humbel, Abel Suarez-Fueyo, Abhigyan Satyam, Nobuya Yoshida, Vasileios C. Kyttaris, Maria G. Tsokos, George C. Tsokos

Nature Communications 15 ( 1 ) 2024.9

Expanded CD8+CD38+ T Cell Population in Patients With Systemic Lupus Erythematosus Is Linked to Increased Infection Rates: A Prospective Study. International journal

Jose Rubio, Morgane Humbel, Lama Mulki, Eri Katsuyama, Suzanne Krishfield, Julianne O'Connell, George C Tsokos, Vasileios Kyttaris

ACR open rheumatology 2024.8

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: One of the leading causes of morbidity and mortality among patients with systemic lupus erythematosus (SLE) is infections. The expression of the ectonucleotidase CD38 on the surface of CD8+ T cells has been linked to compromised cytotoxic function. The aim of this prospective study was to assess whether the presence of CD8+CD38+ in the peripheral blood of patients with SLE can serve as a biomarker for infectious complications. METHODS: A cohort of 80 patients with SLE were recruited over 18 months. The rate of clinically significant infections and presence of CD8+CD38+ T cells in the peripheral blood were monitored at each clinic visit. The patients were classified into high CD38+ and low CD38+ CD8+ T cells using flow cytometry and a previously established cutoff rate of 28.4%. RESULTS: A total of 20 infections were registered over the study period. We observed that the patients with an expanded CD8+CD38+ T cell population in the peripheral blood had a higher rate of recurrent infections and a higher likelihood of infection compared with patients with a low CD8+CD38+ T cell population. The levels of CD38 in CD8+ T cells remained stable over time in the studied subjects. CONCLUSION: High levels of CD8+CD38+ T cells in the peripheral blood of patients with SLE identify a subgroup prone to infections for whom proper clinical measures should be applied.

DOI： 10.1002/acr2.11725

Discontinuity of care and trust in usual physician among patients with systemic lupus erythematosus

Katayama Yu, Miyawaki Yoshia, Shidahara Kenta, Nawachi Shoichi, Asano Yosuke, Katsuyama Eri, Katsuyama Takayuki, Takano-Narazaki Mariko, Matsumoto Yoshinori, Oguro Nao, Ishikawa Yuichi, Sakurai Natsuki, Hidekawa Chiharu, Ohno Shigeru, Ichikawa Takanori, Kishida Dai, Shimojima Yasuhiro, Sada Ken-ei, Wada Jun, Thom David, Kurita Noriaki† (†last author)

medRxiv 2024.03.13.24304255 2024.3

漿液性網膜剥離と蛋白漏出胃腸症を合併した全身性エリテマトーデスの一例

都明希, 勝山隆行, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 片山祐, 宮脇義亜, 勝山恵理, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 914 - 914 2024.3

TAFRO症候群に緩徐進行1型糖尿病を合併した1例

喜舎場朝基, 片山祐, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 914 - 914 2024.3

重症感染症を合併した難治性中小型血管炎に対してアバコパンとγグロブリン大量静注療法(IVIG)で寛解導入に至った1例

小松原悠, 松本佳則, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 片山祐, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 913 - 913 2024.3

婦人科悪性腫瘍の摘出後,速やかにCKが正常化したHMGCR抗体陽性壊死性ミオパチーの一例

古山怜奈, 勝山恵理, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 915 - 915 2024.3

Pseudo pseudo Meigs syndromeを呈したSLEの1例

中山菜々子, 片山祐, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 914 - 914 2024.3

上腸間膜動脈周囲軟部影から血管炎が疑われたが膵癌と判明した一例

志田原健太, 片山祐, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 中土井崇人, 縄稚翔一, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 881 - 881 2024.3

二次性の結節性多発動脈炎の発症したびまん性大細胞型B細胞性リンパ腫の一例

久保田菜月, 宮脇義亜, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 中土井崇人, 縄稚翔一, 片山祐, 勝山隆行, 勝山恵理, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 821 - 821 2024.3

骨免疫制御蛋白に着目した関節リウマチ病態形成メカニズムの解明

三前英恵, 松本佳則, 松本和也, 浅野洋介, 久保田菜月, 寺嶋悠也, 廣瀬啓, 縄稚翔一, 志田原健太, 中土井崇人, 片山祐, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 910 - 910 2024.3

中小型血管炎:治療3 リツキシマブ1000mgの2回投与により寛解導入を行なった初発の顕微鏡的多発血管炎および多発血管炎性肉芽腫症の8例に関する記述研究

松本和也, 宮脇義亜, 久保田菜月, 寺嶋悠也, 廣瀬啓, 志田原健太, 中土井崇人, 縄稚翔一, 片山祐, 勝山隆行, 勝山恵理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 581 - 581 2024.3

不全型ベーチェット病に急性尿細管間質性腎炎を合併した一例

有地萌音, 勝山恵理, 久保田菜月, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 909 - 909 2024.3

好酸球性多発血管炎性肉芽腫症(EGPA)との鑑別に苦慮した好酸球性大腸炎(EoC)の一例

寺嶋悠也, 宮脇義亜, 久保田菜月, 松本和也, 廣瀬啓, 志田原健太, 中土井崇人, 縄稚翔一, 片山祐, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 68回 889 - 889 2024.3

The first presentation of a case of nail-patella syndrome newly diagnosed at the onset of rheumatoid arthritis: a case report. International journal

Kazuya Matsumoto, Yoshinori Matsumoto, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Takayuki Katsuyama, Eri Katsuyama, Yoshihisa Nasu, Ken-Ei Sada, Jun Wada

BMC musculoskeletal disorders 25 ( 1 ) 139 - 139 2024.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal dominant disorder that is characterized by dysplasia of the nails, hypoplasia and/or dislocation of the patella and the presence of iliac horns. Using the CARE guidelines, we present the first reported case of NPS that was newly diagnosed at the onset of rheumatoid arthritis (RA). CASE PRESENTATION: A 74-year-old man was admitted to our hospital due to an 8-month history of arthralgia in bilateral wrists, elbows and fingers. He had a past history of glaucoma and left patella dislocation that had been operatively recentered at the age of 15 years. Laboratory data showed elevated levels of serum C-reactive protein and rheumatoid factor and an elevated titer of anti-SS-A antibodies, while estimated glomerular filtration rate (eGFR), titers of other antibodies and the results of a urinary test were normal. An X-ray showed deformity of bilateral radial heads and the right elbow, and magnetic resonance imaging (MRI) of his hands showed synovitis and erosion in the multiple swollen joints of the wrists and fingers. In addition to these typical features of RA, he had bilateral thumb nail dysplasia with mild hypoplasia of bilateral patellae and iliac horns as shown by the X-ray. He was diagnosed as having autosomal dominant disorder NPS co-existing with RA and he was treated with methotrexate in combination with an oral Janus kinase (JAK) inhibitor, leading to induction of remission. CONCLUSIONS: We have presented a rare case of NPS that was newly diagnosed at the onset of RA. Clinical and radiographic findings of NPS are highlighted in this case report for diagnosing NPS on the basis of typical manifestations.

DOI： 10.1186/s12891-024-07242-2

Infliximab biosimilar-induced lupus nephritis: A case report. International journal

Kenta Shidahara, Takayuki Katsuyama, Kei Hirose, Kazuya Matsumoto, Shoichi Nawachi, Takato Nakadoi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Eri Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

Modern rheumatology case reports 2023.10

Language：English Publishing type：Research paper (scientific journal)

We present a case of microhematuria, proteinuria and hypocomplementemia that developed in a 55-year-old female who was being treated with an infliximab biosimilar (IFX-BS) for rheumatoid arthritis (RA). Renal biopsy showed lupus nephritis (ISN/RPS classification class IV+V). Treatment with the IFX-BS was discontinued, and treatment with prednisolone, hydroxychloroquine and abatacept was started, resulting in clinical remission of lupus nephritis and RA. Although tumor necrosis factor-α (TNF-α) inhibitors are known to induce production of autoantibodies, symptoms are usually limited to skin involvement or arthritis, and renal complications are rare. Physicians should be aware of the risk of lupus nephritis and carefully monitor patients for the development of renal involvement during treatment with TNF-α inhibitors.

DOI： 10.1093/mrcr/rxad061

Immunosuppressive Treatment for an anti-U1 Ribonucleoprotein Antibody-positive Patient with Pulmonary Arterial Hypertension: A Case Report.

Kazuya Matsumoto, Yoshia Miyawaki, Takayuki Katsuyama, Takato Nakadoi, Kenta Shidahara, Kei Hirose, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Eri Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Atsushi Mori, Satoshi Akagi, Ken-Ei Sada, Jun Wada

Internal medicine (Tokyo, Japan) 2023.7

Language：English Publishing type：Research paper (scientific journal)

A 34-year-old woman with pulmonary arterial hypertension (PAH) was admitted to the hospital. She had been diagnosed with PAH three years earlier and treated with triple vasodilator therapy. She was positive for anti-U1 ribonucleoprotein antibodies but did not show any other symptoms associated with autoimmune diseases. Corticosteroid and cyclophosphamide therapy was administered, suspecting the involvement of immunological pathophysiology. After 3 weeks, the mean pulmonary artery pressure decreased from 50 to 38 mmHg without any change in the vasodilators. Immunosuppressive therapy was effective in this patient with PAH with an anti-U1 ribonucleoprotein-antibody-positive response and might be an option for patients with these specific features.

DOI： 10.2169/internalmedicine.1407-22

脱毛から診断に至った高齢期発症の全身性エリテマトーデスの1例

岡野真理, 横山恵美, 川上佳夫, 森実真, 勝山恵理, 山口春佳

日本皮膚科学会雑誌 133 ( 8 ) 1892 - 1892 2023.7

今年も開催!!行列のできる診療所第3弾:脂質異常症難病ケーススタディ高安動脈炎が疑われたがPET-CTを契機に希少疾患であるシトステロール血症と判明した一例

中土井崇人, 勝山恵理, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 多田隼人, 和田淳

日本動脈硬化学会総会プログラム・抄録集 55回 130 - 130 2023.6

The Association of Grit With Burnout Components (Professional Efficacy, Exhaustion, and Cynicism) Among Academic Rheumatologists: The TRUMP2-SLE Study. International journal

Yoshia Miyawaki, Ken-Ei Sada, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Keigo Hayashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nao Oguro, Nobuyuki Yajima, Yuichi Ishikawa, Natsuki Sakurai, Chiharu Hidekawa, Ryusuke Yoshimi, Takanori Ichikawa, Dai Kishida, Yasuhiro Shimojima, Jun Wada, Noriaki Kurita

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 29 ( 6 ) 268 - 274 2023.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists. METHODS: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [associate professor or higher vs lower], marital status, and having children). RESULTS: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04). CONCLUSIONS: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit.

DOI： 10.1097/RHU.0000000000001989

Amelioration of nephritis in receptor for advanced glycation end-products (RAGE)-deficient lupus-prone mice through neutrophil extracellular traps. International journal

Haruki Watanabe, Masataka Kubo, Akihiko Taniguchi, Yosuke Asano, Sumie Hiramatsu-Asano, Keiji Ohashi, Sonia Zeggar, Eri Katsuyama, Takayuki Katsuyama, Katsue Sunahori-Watanabe, Ken-Ei Sada, Yoshinori Matsumoto, Yasuhiko Yamamoto, Hiroshi Yamamoto, Myoungsun Son, Jun Wada

Clinical immunology (Orlando, Fla.) 250 109317 - 109317 2023.5

Language：English Publishing type：Research paper (scientific journal)

The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor that regulates inflammation, cell migration, and cell fate. Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease. To understand the function of RAGE in SLE, we generated RAGE-deficient (Ager-/-) lupus-prone mice by backcrossing MRL/MpJ-Faslpr/J (MRL-lpr) mice with Ager-/- C57BL/6 mice. In 18-week-old Ager-/- MRL-lpr, the weights of the spleen and lymph nodes, as well as the frequency of CD3+CD4-CD8- cells, were significantly decreased. Ager-/- MRL-lpr mice had significantly reduced urine albumin/creatinine ratios and markedly improved renal pathological scores. Moreover, neutrophil infiltration and neutrophil extracellular trap formation in the glomerulus were significantly reduced in Ager-/- MRL-lpr. Our study is the first to reveal that RAGE can have a pathologic role in immune cells, particularly neutrophils and T cells, in inflammatory tissues and suggests that the inhibition of RAGE may be a potential therapeutic strategy for SLE.

DOI： 10.1016/j.clim.2023.109317

プラスミノーゲン欠乏症に腸管型ベーチェット病を合併し広範な皮膚粘膜病変を発症した一例

中土井崇人, 勝山恵理, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 大塚文男, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 795 - 795 2023.3

中耳炎再燃を繰り返し,ANCA陰性であったがANCA関連血管炎性中耳炎(OMAAV)の診断に至った2例

志田原健太, 松本佳則, 寺嶋悠也, 廣瀬啓, 松本和也, 中土井崇人, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 790 - 790 2023.3

皮膚筋炎加療中に重篤なBordetella bronchiseptica肺炎,菌血症を呈した一例

寺嶋悠也, 片山祐, 松本和也, 廣瀬啓, 志田原健太, 中土井崇人, 縄稚翔一, 浅野洋介, 宮脇義亜, 勝山隆行, 勝山恵理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 852 - 852 2023.3

多発性筋炎・皮膚筋炎5:筋病変嚥下機能障害を伴う炎症性筋疾患,その臨床的特徴と予後についての検討

勝山隆行, 宮脇義亜, 寺嶋悠也, 中土井崇人, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 勝山惠理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 643 - 643 2023.3

難治性病態への挑戦免疫抑制療法が有効であった抗RNP抗体陽性の特発性肺動脈性肺高血圧症の一例

松本和也, 宮脇義亜, 勝山隆行, 中土井崇人, 志田原健太, 廣瀬啓, 縄稚翔一, 浅野洋介, 片山祐, 勝山恵理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 720 - 720 2023.3

SLE(ヒドロキシクロロキン・その他) SLE患者の心理的健康観の最小重要差と副腎皮質ステロイド量の検討多施設共同前向きコホート研究(Lupus registry of Nationwide institutions:LUNA)

宮脇義亜, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 柳井亮, 矢嶋宣幸, 高谷亜由子, 一瀬邦弘, 梶山浩, 西村啓佑, 木田節, 下島恭弘, 吉見竜介, 大野滋, 大西貴久, 佐藤秀三, 藤原道雄, 松尾祐介, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 660 - 660 2023.3

高齢発症SLEの脱毛が著明に改善した1例

秋山万里子, 勝山恵理, 中土井崇人, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 915 - 915 2023.3

COVID-19罹患後に発症した抗MDA5抗体陽性皮膚筋炎の一例

樋口朝涼香, 勝山隆行, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 宮脇義亜, 勝山恵理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 914 - 914 2023.3

全身性エリテマトーデス(SLE)治療中に下腿浮腫、下肢運動障害が出現したサイトメガロ(CMV)脳脊髄炎の一例

齋藤光希, 松本佳則, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 928 - 928 2023.3

インフリキシマブ投与中に内臓播種性帯状疱疹を発症した腸管ベーチェット病の1例

大久保茉柚, 片山祐, 寺嶋悠也, 志田原健太, 廣瀬啓, 松本和也, 中土井崇人, 縄稚翔一, 浅野洋介, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 916 - 916 2023.3

膵尾部腫瘤の切除後8年経過し,冠動脈周囲炎と心嚢液貯留を契機に診断されたIgG4関連疾患の1例

縄稚翔一, 勝山恵理, 寺嶋悠也, 廣瀬啓, 松本和也, 志田原健太, 中土井崇人, 浅野洋介, 片山祐, 宮脇義亜, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 897 - 897 2023.3

再燃を繰り返しPET-CTで右冠動脈周囲B細胞性リンパ腫の診断に至った抗TIF1-γ抗体陽性皮膚筋炎の一例

廣瀬啓, 勝山隆行, 寺嶋悠也, 松本和也, 志田原健太, 中土井崇人, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 勝山恵理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 888 - 888 2023.3

多発血管炎性肉芽腫症(GPA)に対してリツキシマブ投与中にカンピロバクター菌血症を発症した一例

川嶋帆乃, 縄稚翔一, 寺嶋悠也, 廣瀬啓, 松本和也, 志田原健太, 中土井崇人, 浅野洋介, 片山祐, 宮脇義亜, 勝山隆行, 勝山恵理, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 914 - 914 2023.3

ベーチェット病様症状を呈したパルボウィルスB19感染症の一例

物部祥子, 松本佳則, 寺嶋悠也, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 67回 914 - 914 2023.3

Association of alcohol consumption and fatigue in SLE: A cross-sectional study from Lupus Registry of Nationwide Institution (LUNA) cohort. International journal

Yu Katayama, Yoshia Miyawaki, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Keiji Ohashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Nobuyuki Yajima, Yasuhiro Shimojima, Ryusuke Yoshimi, Kunihiro Ichinose, Hiroshi Kajiyama, Michio Fujiwara, Shuzo Sato, Jun Wada

Lupus 32 ( 4 ) 9612033231159471 - 9612033231159471 2023.2

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Fatigue is one of the most common complaints and is a potentially modifiable issue in systemic lupus erythematosus (SLE). Studies suggest that alcohol consumption has a protective effect against the development of SLE; however, an association between alcohol consumption and fatigue in patients with SLE has not been studied. Here, we assessed whether alcohol consumption was associated with fatigue using lupus patient-reported outcomes (LupusPRO). METHODS: This cross-sectional study, conducted between 2018 and 2019, included 534 patients (median age, 45 years; 87.3% female) from 10 institutions in Japan. The main exposure was alcohol consumption, which was defined as the frequency of drinking [<1 day/month (none group), ≤1 day/week (moderate group), and ≥2 days/week (frequent group)]. The outcome measure was the Pain Vitality domain score in LupusPRO. Multiple regression analysis was performed as the primary analysis after adjusting for confounding factors, such as age, sex, and damage. Subsequently, the same analysis was performed as a sensitivity analysis after multiple imputations (MIs) for missing data (n = 580). RESULTS: In total, 326 (61.0%) patients were categorized into the none group, 121 (22.7%) into the moderate group, and 87 (16.3%) into the frequent group. The frequent group was independently associated with less fatigue compared with none group [β = 5.98 (95% CI 0.19-11.76), p = 0.04], and the results did not substantially deviate after MI. CONCLUSIONS: Frequent drinking was associated with less fatigue, which highlights the need for further longitudinal studies focusing on drinking habits in patients with SLE.

DOI： 10.1177/09612033231159471

A young female case of asymptomatic immune-mediated necrotizing myopathy: a potential diagnostic option of antibody testing for rhabdomyolysis. International journal

Ryo Sasaki, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Eri Katsuyama, Ichizo Nishino, Toru Yamashita

Neuromuscular disorders : NMD 33 ( 2 ) 183 - 186 2023.2

Language：English

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) is a neuromuscular disorder that presents muscle weakness in proximal extremities and/or the trunk with an elevation of creatine kinase (CK). Young and asymptomatic anti-HMGCR IMNM patients are very rare and a treatment regimen has not been established. The present case, a 17-year-old woman without any muscular symptoms, only showed hyperCKemia that was detected by chance. After close examinations, including a muscle biopsy and antibody search, she was diagnosed as anti-HMGCR IMNM, and initial treatment with methotrexate and continuous intravenous immunoglobulin seemed to be effective. The present case is the unusually young asymptomatic case of anti-HMGCR IMNM. The diagnosis was successfully made, leading to the early introduction of a treatment. Given the course of this case, we believe that the preceding antibody testing is one of the diagnostic option for rhabdomyolysis.

DOI： 10.1016/j.nmd.2022.12.012

Pharmacologic inhibition of PARP5, but not that of PARP1 or 2, promotes cytokine production and osteoclastogenesis through different pathways. International journal

Yosuke Asano, Yoshinori Matsumoto, Fang He, Takayuki Katsuyama, Eri Katsuyama, Shigetomo Tsuji, Hiroshi Kamioka, Jose La Rose, Robert Rottapel, Jun Wada

Clinical and experimental rheumatology 41 ( 9 ) 1735 - 1745 2023.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: PARPs, which are members of the poly(ADP-ribose) polymerase superfamily, promote tumorigenesis and tumour-associated inflammation and are thus therapeutic targets for several cancers. The aim of the present study is to investigate the mechanistic insight into the roles PARPs for inflammation. METHODS: Primary murine macrophages were cultured in the presence or absence of the PARP5 inhibitor NVP-TNKS656 to examine the role of PARP5 for cytokine production. RESULTS: In contrast to the roles of other PARPs for induction of inflammation, we found in the present study that pharmacologic inhibition of PARP5 induces production of inflammatory cytokines in primary murine macrophages. We found that treatment with the PARP5 inhibitor NVP-TNKS656 in macrophages enhanced steady-state and LPS-mediated cytokine production through degradation of IκBα and subsequent nuclear translocation of NF-κB. We also found that pharmacologic inhibition of PARP5 stabilises the adaptor protein 3BP2, a substrate of PARP5, and that accelerated cytokine production induced by PARP5 inhibition was rescued in 3BP2-deleted macrophages. Additionally, we found that LPS increases the expression of 3BP2 and AXIN1, a negative regulator of β-catenin, through suppression of PARP5 transcripts in macrophages, leading to further activation of cytokine production and inhibition of β-catenin-mediated cell proliferation, respectively. Lastly, we found that PARP5 inhibition in macrophages promotes osteoclastogenesis through stabilisation of 3BP2 and AXIN1, leading to activation of SRC and suppression of β-catenin, respectively. CONCLUSIONS: Our results show that pharmacologic inhibition of PARP5 against cancers unexpectedly induces adverse autoinflammatory side effects through activation of innate immunity, unlike inhibition of other PARPs.

DOI： 10.55563/clinexprheumatol/qf55h8

A case of sitosterolaemia-caused systemic large-vessel stenosis mimicking Takayasu arteritis in which FDG-PET provided a clue for the differential diagnosis

Takato Nakadoi, Eri Katsuyama, Kazuya Matsumoto, Kenta Shidahara, Kei Hirose, Shoichi Nawachi, Yosuke Asano, Yu Katayama, Yoshia Miyawaki, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Hayato Tada, Jun Wada

Rheumatology Advances in Practice 7 ( 3 ) 2023.1

Grit personality of physicians and achievement of treatment goals in patients with systemic lupus erythematosus. International journal

Ken-Ei Sada, Yoshia Miyawaki, Kenta Shidahara, Shoichi Nawachi, Yu Katayama, Yosuke Asano, Keigo Hayashi, Keiji Ohashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Nao Oguro, Yuichi Ishikawa, Natsuki Sakurai, Chiharu Hidekawa, Ryusuke Yoshimi, Dai Kishida, Takanori Ichikawa, Yasuhiro Shimojima, Noriaki Kurita, Nobuyuki Yajima

Rheumatology (Oxford, England) 62 ( 6 ) 2154 - 2159 2022.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Although personality characteristics of patients with systemic lupus erythematosus (SLE) affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. METHODS: This cross-sectional study was conducted at five referral hospitals. The main exposure was "consistency of interest" and "perseverance of effort" of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analyzed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation with adjustment for confounders. RESULTS: The median (interquartile range) total, consistency, and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8), and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question "I often set a goal but later choose to pursue a different one" was significantly higher in patients achieving LLDAS. CONCLUSIONS: Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.

DOI： 10.1093/rheumatology/keac612

A case of recurrent IgG4-related disease successfully treated with belimumab after remission of systemic lupus erythematosus. International journal

Yu Katayama, Takayuki Katsuyama, Kenta Shidahara, Shoichi Nawachi, Yosuke Asano, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Ken-Ei Sada, Jun Wada

Rheumatology (Oxford, England) 61 ( 10 ) e308-e310 2022.10

Association of one-point glucocorticoid-free status with chronic damage and disease duration in systemic lupus erythematosus: a cross-sectional study. International journal

Ken-Ei Sada, Yu Katayama, Yosuke Asano, Keigo Hayashi, Yoshia Miyawaki, Keiji Ohashi, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano-Narazaki, Yoshinori Matsumoto, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Nobuyuki Yajima

Lupus science & medicine 9 ( 1 ) 2022.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status. METHODS: Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5-20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index. RESULTS: GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0<prednisolone (PSL) ≤5 mg/day in 411 (40%); 5<PSL ≤7.5 in 169 (17%); 7.5<PSL ≤10 in 194 (19%) and PSL≥10 in 144 (14%) patients. Of the patients who were not currently using GCs, patients who never used GC more frequently had short disease duration (66% with short, 23% with middle and 17% with long disease duration, p=0.00029). Univariate analysis of patients who underwent GC treatment showed that patients without GCs exhibited older age, lower disease activity, less immunosuppressant and hydroxychloroquine use and higher C3 levels. Among patients with a disease duration of ≥20 years, GC-free status was more frequent in patients without chronic damage (11% vs 4%, p=0.023). After adjusting for age, sex and disease activity, no chronic damage accrual was associated with GC-free status (OR 3.6, 95% CI 1.1 to 11.3). CONCLUSION: Even in the patients with long disease duration, one-point GC-free treatment status might be related to no chronic damage accrual.

DOI： 10.1136/lupus-2022-000772

CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy. International journal

Ping-Min Chen, Eri Katsuyama, Abhigyan Satyam, Hao Li, Jose Rubio, Sungwook Jung, Sylvia Andrzejewski, J David Becherer, Maria G Tsokos, Reza Abdi, George C Tsokos

Science advances 8 ( 24 ) eabo4271 2022.6

Language：English Publishing type：Research paper (scientific journal)

Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD+, is up-regulated in CD8+ T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8+ T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8+ T cell-targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.

DOI： 10.1126/sciadv.abo4271

関節リウマチの増悪との鑑別に苦慮した両側踵脆弱性骨折の1例

氏家正皓, 片山祐, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 松本佳則, 中原龍一, 那須義久, 西田圭一郎, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 753 - 753 2022.3

IgG4関連肥厚性硬膜炎に重篤な視力障害を来たし視神経周囲炎が示唆された一例

上舞直, 宮脇義亜, 松本和也, 中土井崇人, 大橋敬司, 廣瀬啓, 縄稚翔一, 志田原健太, 浅野洋介, 片山祐, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 754 - 754 2022.3

初発から40年後に診断に至った炎症症候持続TNF受容体関連周期性症候群の一例

高嶋香菜子, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

Clinical manifestations of SLE SLE患者における代診医師への受診と主治医への信頼度との関連性 TRUMP2-SLEの横断研究(The Association of the visits to substitute physicians and trust in one's physician in SLE patients: a cross-sectional TRUMP2-SLE study)

Katayama Yu, Miyawaki Yoshia, Shidahara Kenta, Nawachi Shoichi, Asano Yosuke, Ohashi Keiji, Katsuyama Eri, Katsuyama Takayuki, Narazaki Mariko, Matsumoto Yoshinori, Sada Ken-ei, Oguro Nao, Yajima Nobuyuki, Yoshimi Ryusuke, Shimojima Yasuhiro, Wada Jun, Kurita Nobuaki

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 503 - 503 2022.3

痛風性関節炎、特発性間質性肺炎発症後に多発脳梗塞を呈した顕微鏡的多発血管炎(MPA)の1例

堀口裕紀, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

SLEにおける疾患活動性とQOL SLE患者の健康関連QOL指標の解釈を可能にする最小重要差の検討前向きコホート研究から登録時記述疫学

松本和也, 宮脇義亜, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 柳井亮, 矢嶋宣幸, 高谷亜由子, 一瀬邦弘, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 367 - 367 2022.3

横隔膜挙上に伴う呼吸困難を合併した巨細胞性動脈炎(GCA)の一例

松岡雅人, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 755 - 755 2022.3

COVID-19ワクチン接種後に脊椎関節炎が顕在化した一例

志田原健太, 松本佳則, 松本和也, 廣瀬啓, 中土井崇人, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 627 - 627 2022.3

IgG4関連肥厚性硬膜炎に重篤な視力障害を来たし視神経周囲炎が示唆された一例

上舞直, 宮脇義亜, 松本和也, 中土井崇人, 大橋敬司, 廣瀬啓, 縄稚翔一, 志田原健太, 浅野洋介, 片山祐, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 754 - 754 2022.3

高安動脈炎が疑われたがPET-CTを契機に希少疾患であるシトステロール血症と判明した一例

中土井崇人, 勝山恵理, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 大橋敬司, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 672 - 672 2022.3

動眼神経麻痺を発症した巨細胞性動脈炎の一例

清水崇司, 勝山隆行, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 楢崎真理子, 佐田憲映, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 755 - 755 2022.3

爪形成不全と肘関節脱臼を伴った関節リウマチの1例

増田倫敦, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 754 - 754 2022.3

大型血管炎が疑われた大動脈周囲悪性リンパ腫の1例

道廣麻友, 勝山隆行, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 楢崎真理子, 佐田憲映, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

SLEにおける疾患活動性とQOL 全身性エリテマトーデス診療における医師の性格特性と治療目標達成との関連 TRUMP2-SLE研究

佐田憲映, 宮脇義亜, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 勝山隆行, 勝山恵理, 楢崎真理子, 松本佳則, 小黒奈緒, 矢嶋宣幸, 吉見竜介, 下島恭弘, 栗田宜明

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 367 - 367 2022.3

痛風性関節炎、特発性間質性肺炎発症後に多発脳梗塞を呈した顕微鏡的多発血管炎(MPA)の1例

堀口裕紀, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

横隔膜挙上に伴う呼吸困難を合併した巨細胞性動脈炎(GCA)の一例

松岡雅人, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 755 - 755 2022.3

大型血管炎が疑われた大動脈周囲悪性リンパ腫の1例

道廣麻友, 勝山隆行, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 楢崎真理子, 佐田憲映, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

初発から40年後に診断に至った炎症症候持続TNF受容体関連周期性症候群の一例

高嶋香菜子, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

高安動脈炎が疑われたがPET-CTを契機に希少疾患であるシトステロール血症と判明した一例

中土井崇人, 勝山恵理, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 大橋敬司, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 672 - 672 2022.3

COVID-19ワクチン接種後に脊椎関節炎が顕在化した一例

志田原健太, 松本佳則, 松本和也, 廣瀬啓, 中土井崇人, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 627 - 627 2022.3

動眼神経麻痺を発症した巨細胞性動脈炎の一例

清水崇司, 勝山隆行, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 楢崎真理子, 佐田憲映, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 755 - 755 2022.3

爪形成不全と肘関節脱臼を伴った関節リウマチの1例

増田倫敦, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 754 - 754 2022.3

臨床(内科)・症例報告大学病院に勤務する膠原病・リウマチ内科医のバーンアウト(燃え尽き症候群)とグリットとの関連 TRUMP2-SLE研究

宮脇義亜, 佐田憲映, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 小黒奈緒, 矢嶋宣幸, 吉見竜介, 下島恭弘, 和田淳, 栗田宜明

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 435 - 435 2022.3

Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study. International journal

Junko Inagaki, Airi Nakano, Omer Faruk Hatipoglu, Yuka Ooka, Yurina Tani, Akane Miki, Kentaro Ikemura, Gabriel Opoku, Ryosuke Ando, Shintaro Kodama, Takashi Ohtsuki, Hirosuke Yamaji, Shusei Yamamoto, Eri Katsuyama, Shogo Watanabe, Satoshi Hirohata

International journal of molecular sciences 23 ( 5 ) 2022.2

Language：English Publishing type：Research paper (scientific journal)

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1β-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1β-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints.

DOI： 10.3390/ijms23052681

Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity. International journal

Rodrigo W Alves de Souza, David Gallo, Ghee Rye Lee, Eri Katsuyama, Alexa Schaufler, Janick Weber, Eva Csizmadia, George C Tsokos, Lauren G Koch, Steven L Britton, Ulrik Wisløff, Patricia C Brum, Leo E Otterbein

Cell reports 35 ( 3 ) 109018 - 109018 2021.4

Language：English Publishing type：Research paper (scientific journal)

Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.

DOI： 10.1016/j.celrep.2021.109018

Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study. International journal

Eri Katsuyama, Yoshia Miyawaki, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu-Asano, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Jun Wada

BMC nephrology 21 ( 1 ) 208 - 208 2020.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). METHODS: In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. RESULTS: The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). CONCLUSION: As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

DOI： 10.1186/s12882-020-01868-9

Risk Factors for Chronic Damage Accumulation Across Different Onset Eras in Systemic Lupus Erythematosus: A Cross-sectional Analysis of a Lupus Registry of Nationwide Institutions (LUNA).

Keiji Ohashi, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu Asano, Yoshia Miyawaki, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori-Watanabe, Tomoko Kawabata, Nobuyuki Yajima, Jun Wada

Acta medica Okayama 74 ( 3 ) 191 - 198 2020.6

Language：English Publishing type：Research paper (scientific journal)

Chronic damage accumulation affects not only mortality but also quality of life in patients with systemic lupus erythematosus (SLE). Risk factors for chronic damage were explored in SLE through different onset eras. Two hundred forty-five patients at Okayama University Hospital and Showa University Hospital were divided into three groups based on the onset era: a past-onset group (onset before 1995; n=83), middle-onset group (1996-2009; n=88), and recent-onset group (after 2010; n=74). The mean Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score as an index of chronic damage was 1.93, 1.24, and 0.53 in the past-, middle-, and recent-onset groups, respectively. In the pastonset group, the total SDI score was significantly associated with glucocorticoid monotherapy by linear regression analysis (β-coefficient [β]=0.63; 95% confidence interval [CI], 0.21-1.05) and C-reactive protein levels (β=0.67; 95% CI, 0.27-1.07). In the middle-onset group, the total SDI score was significantly associated with the SLE Disease Activity Index at registration (β=0.09; 95% CI, 0.03-0.12). Reducing the accumulation of chronic damage in SLE patients might be possible with the concomitant use of immunosuppressants and tight control of disease activity.

DOI： 10.18926/AMO/59949

The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections. International journal

Eri Katsuyama, Abel Suarez-Fueyo, Sean J Bradley, Masayuki Mizui, Ana V Marin, Lama Mulki, Suzanne Krishfield, Fabio Malavasi, Joon Yoon, Shannan J Ho Sui, Vasileios C Kyttaris, George C Tsokos

Cell reports 30 ( 1 ) 112 - 123 2020.1

Language：English Publishing type：Research paper (scientific journal)

Patients with systemic lupus erythematosus (SLE) suffer frequent infections that account for significant morbidity and mortality. T cell cytotoxic responses are decreased in patients with SLE, yet the responsible molecular events are largely unknown. We find an expanded CD8CD38high T cell subset in a subgroup of patients with increased rates of infections. CD8CD38high T cells from healthy subjects and patients with SLE display decreased cytotoxic capacity, degranulation, and expression of granzymes A and B and perforin. The key cytotoxicity-related transcription factors T-bet, RUNX3, and EOMES are decreased in CD8CD38high T cells. CD38 leads to increased acetylated EZH2 through inhibition of the deacetylase Sirtuin1. Acetylated EZH2 represses RUNX3 expression, whereas inhibition of EZH2 restores CD8 T cell cytotoxic responses. We propose that high levels of CD38 lead to decreased CD8 T cell-mediated cytotoxicity and increased propensity to infections in patients with SLE, a process that can be reversed pharmacologically.

DOI： 10.1016/j.celrep.2019.12.014

Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr/lpr Mice. International journal

Sumie Hiramatsu-Asano, Katsue Sunahori-Watanabe, Sonia Zeggar, Eri Katsuyama, Tomoyuki Mukai, Yoshitaka Morita, Jun Wada

Frontiers in immunology 11 616141 - 616141 2020

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. METHODS: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223-/-Faslpr/lpr mice and the lupus phenotypes were analyzed. RESULTS: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr /J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3' UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223-/-Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8- cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223+/+Faslpr/lpr mice by flow cytometry. B6-Mir223-/-Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. CONCLUSION: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.

DOI： 10.3389/fimmu.2020.616141

Cluster Analysis Using Anti-Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis. International journal

Keiji Ohashi, Ken-Ei Sada, Yu Nakai, Shun Matsushima, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori Watanabe, Tomoko Kawabata, Jun Wada

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 25 ( 6 ) 246 - 251 2019.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated. METHODS: Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters. RESULTS: Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2. CONCLUSIONS: Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.

DOI： 10.1097/RHU.0000000000000836

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer. International journal

Burcu Yigit, Ninghai Wang, Elisa Ten Hacken, Shih-Shih Chen, Atul K Bhan, Abel Suarez-Fueyo, Eri Katsuyama, George C Tsokos, Nicholas Chiorazzi, Catherine J Wu, Jan A Burger, Roland W Herzog, Pablo Engel, Cox Terhorst

Cancer immunology research 7 ( 9 ) 1485 - 1496 2019.9

Language：English Publishing type：Research paper (scientific journal)

The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8+ cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the Eμ-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell-surface receptor SLAMF6 as an immune-checkpoint regulator. The transfer of SLAMF6+ Eμ-TCL1 cells into SLAMF6-/- recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1+ subpopulation among CD3+CD44+CD8+ T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in Eμ-TCL1 recipient WT mice concomitantly with a loss of PD-1+CD3+CD44+CD8+ T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8+ T cells. Targeting of SLAMF6 affected tumor growth not only in B cell-related leukemia and lymphomas but also in nonhematopoietic tumors such as B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8+ T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8+ T-cell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy.

DOI： 10.1158/2326-6066.CIR-18-0664

Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation. International journal

Michihito Kono, Kayaho Maeda, Irina Stocton-Gavanescu, Wenliang Pan, Masataka Umeda, Eri Katsuyama, Catalina Burbano, Seo Yeon K Orite, Milena Vukelic, Maria G Tsokos, Nobuya Yoshida, George C Tsokos

JCI insight 4 ( 12 ) 2019.6

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1172/jci.insight.127395

Regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice derived CD4+ T cells. Reviewed International journal

Sumie Hiramatsu, Katsue S Watanabe, Sonia Zeggar, Yosuke Asano, Yoshia Miyawaki, Yuriko Yamamura, Eri Katsuyama, Takayuki Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

Scientific reports 9 ( 1 ) 3054 - 3054 2019.2

Language：English Publishing type：Research paper (scientific journal)

Global DNA hypomethylation in CD4+ cells in systemic lupus erythematosus (SLE) was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and Ctse mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was 93.3 ± 2.05% methylated in B6 mice, while 80.0 ± 6.2% methylated and mutated to CGGG in MRL mice. Kaiso is known to bind to mCGCG and we hypothesized that it represses expression of Ctse in B6 mice. The binding of Kaiso to mCGCG site in B6 mice was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or Trichostatin A showed the suppression of binding of Kaiso to mCGCG motif by ChIP-PCR and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.

DOI： 10.1038/s41598-019-38809-y

Signaling Lymphocytic Activation Molecule Family Member 1 Engagement Inhibits T Cell-B Cell Interaction and Diminishes Interleukin-6 Production and Plasmablast Differentiation in Systemic Lupus Erythematosus. International journal

Maria P Karampetsou, Denis Comte, Abel Suárez-Fueyo, Eri Katsuyama, Nobuya Yoshida, Michihito Kono, Vasileios C Kyttaris, George C Tsokos

Arthritis & rheumatology (Hoboken, N.J.) 71 ( 1 ) 99 - 108 2019.1

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1002/art.40682

Hyaluronic Acid Synthesis Contributes to Tissue Damage in Systemic Lupus Erythematosus. International journal

Abel Suarez-Fueyo, Maria G Tsokos, Seung-Ki Kwok, Kayaho Maeda, Eri Katsuyama, Peter H Lapchak, George C Tsokos

Frontiers in immunology 10 2172 - 2172 2019

Language：English Publishing type：Research paper (scientific journal)

Hyaluronic acid (HA), a component of the extracellular matrix, is the ligand for CD44 and has been implicated in the pathogenesis of kidney inflammation in patients with systemic lupus erythematosus (SLE), but its direct role and mechanism of action have not been studied. Here we show that administration of hymecromone (4-Methylumbelliferone, 4-MU), an HA synthesis inhibitor, to lupus-prone mice suppressed dramatically lupus-related pathology. Interestingly, 4-MU stopped the appearance of disease when administered prior to its onset and inhibited the progression of disease when administered after its appearance. Inhibition of HA synthesis in vivo reduced tissue damage and the number of intrarenal lymphoid cell infiltrates including double negative CD3+CD4-CD8- T cells which are known to be involved in the pathogenesis of SLE. Exposure of human peripheral blood mononuclear cells to HA in vitro increased the generation of CD3+CD4-CD8- T cells through a mechanism involving Rho-associated kinase. Our results signify the importance of the HA-rich tissue microenvironment in the activation of lymphocytes to cause tissue damage in SLE and suggest the consideration of inhibition of HA synthesis to treat patients.

DOI： 10.3389/fimmu.2019.02172

Risk factors for cytomegalovirus infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis. International journal

Michiko Morishita, Ken-Ei Sada, Yoshinori Matsumoto, Keigo Hayashi, Yosuke Asano, Sumie Hiramatsu Asano, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Haruki Watanabe, Tomoko Kawabata, Jun Wada

PloS one 14 ( 7 ) e0218705 2019

Language：English Publishing type：Research paper (scientific journal)

AIMS: Cytomegalovirus (CMV) infection under immunosuppression sometimes causes death. This study aimed to elucidate risk factors for CMV infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Patients with AAV who underwent remission induction treatment at Okayama University Hospital between 2006 and 2016 were retrospectively analyzed. The primary outcome was the development of CMV infection within 3 months. RESULTS: Of the 111 patients, 13 (11.7%) patients developed CMV infection. Patients with CMV infection were older (p = 0.030) and had a higher body mass index (p = 0.029) in comparison to those without CMV infection. A higher proportion had a severe form (p = 0.001) and granulomatosis with polyangiitis (GPA) (p = 0.001), as well as a higher Birmingham Vasculitis Activity Score (p = 0.018) and C-reactive protein (p = 0.018) levels at baseline. Using logistic regression analysis, severe form and GPA were independent risk factors (odds ratio [OR] = 9.68, 95% confidence interval [CI] = 1.92-60.23, and OR = 7.46, 95% CI = 1.46-47.60, respectively). In addition, patients with CMV infection were more likely than those without infection to be glucocorticoid-related diabetes mellitus (p = 0.025). CONCLUSION: Our study highlights disease severity and subgroups of AAV as risk factors for CMV infection.

DOI： 10.1371/journal.pone.0218705

Metabolomics-based profiles predictive of low bone mass in menopausal women. International journal

Takeshi Miyamoto, Akiyoshi Hirayama, Yuiko Sato, Tami Koboyashi, Eri Katsuyama, Hiroya Kanagawa, Atsuhiro Fujie, Mayu Morita, Ryuichi Watanabe, Toshimi Tando, Kana Miyamoto, Takashi Tsuji, Atsushi Funayama, Tomoyoshi Soga, Masaru Tomita, Masaya Nakamura, Morio Matsumoto

Bone reports 9 11 - 18 2018.12

Language：English Publishing type：Research paper (scientific journal)

Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Low bone mass and/or pre-existing bone fragility fractures serve as diagnostic criteria in deciding when to start medication for osteoporosis. Although osteoporosis is a metabolic disorder, metabolic markers to predict reduced bone mass are unknown. Here, we show serum metabolomics profiles of women grouped as pre-menopausal with normal bone mineral density (BMD) (normal estrogen and normal BMD; NN), post-menopausal with normal BMD (low estrogen and normal BMD; LN) or post-menopausal with low BMD (low estrogen and low BMD; LL) using comprehensive metabolomics analysis. To do so, we enrolled healthy volunteer and osteoporosis patient female subjects, surveyed them with a questionnaire, measured their BMD, and then undertook a comprehensive metabolomics analysis of sera of the three groups named above. We identified 24 metabolites whose levels differed significantly between NN/LN and NN/LL groups, as well as 18 or 10 metabolites whose levels differed significantly between NN/LN and LN/LL, or LN/LL and NN/LN groups, respectively. Our data shows metabolomics changes represent useful markers to predict estrogen deficiency and/or bone loss.

DOI： 10.1016/j.bonr.2018.06.004

Correction: Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells. International journal

Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Mariko Narazaki, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R Moulton, George C Tsokos, Ken-Ei Sada, Jun Wada

Journal of immunology (Baltimore, Md. : 1950) 201 ( 3 ) 1104 - 1104 2018.8

広範囲な全身動脈炎を来したIgG4関連疾患の症例

山村裕理子, 内田成彦, 川畑智子, 林啓悟, 平松澄恵, 森下美智子, 宮脇義亜, 大橋敬司, 勝山恵理, 勝山隆行, 渡辺晴樹, 楢崎真理子, 建部智子, 渡部克枝, 佐田憲映, 和田淳

岡山医学会雑誌 130 ( 2 ) 98 - 98 2018.8

Role of Lgals9 Deficiency in Attenuating Nephritis and Arthritis in BALB/c Mice in a Pristane-Induced Lupus Model. International journal

Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada

Arthritis & rheumatology (Hoboken, N.J.) 70 ( 7 ) 1089 - 1101 2018.7

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvement, the development of lupus nephritis determines prognosis, and arthritis impairs quality of life. Galectin 9 (Gal-9, Lgals9) is a β-galactoside-binding lectin that has been used for clinical application in autoimmune diseases, since recombinant Gal-9, as a ligand for T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), induces apoptosis of activated CD4+TIM-3+ Th1 cells. This study was undertaken to investigate whether deficiency of Lgals9 has beneficial or deleterious effects on lupus in a murine model. METHODS: Gal-9+/+ and Gal-9-/- female BALB/c mice were injected with pristane, and the severity of arthritis, proteinuria, and levels of autoantibody production were assessed at several time points immediately following injection. At 7 months after pristane injection, renal pathologic features, the severity of joint inflammation, and formation of lipogranulomas were evaluated. Subsets of inflammatory cells in the spleen and peritoneal lavage were characterized, and expression levels of cytokines from peritoneal macrophages were analyzed. RESULTS: Lgals9 deficiency protected against the development of immune complex glomerulonephritis, arthritis, and peritoneal lipogranuloma formation in BALB/c mice in this murine model of pristane-induced lupus. The populations of T cell subsets and B cells in the spleen and peritoneum were not altered by Lgals9 deficiency in pristane-injected BALB/c mice. Furthermore, Lgals9 deficiency protected against pristane-induced lupus without altering the Toll-like receptor 7-type I interferon pathway. CONCLUSION: Gal-9 is required for the induction and development of lupus nephritis and arthritis in this murine model of SLE. The results of the current investigation provide a potential new strategy in which antagonism of Gal-9 may be beneficial for the treatment of nephritis and arthritis in patients with SLE through targeting of activated macrophages.

DOI： 10.1002/art.40467

Downregulation of CD3ζ in NK Cells from Systemic Lupus Erythematosus Patients Confers a Proinflammatory Phenotype. International journal

Abel Suárez-Fueyo, Sean J Bradley, Takayuki Katsuyama, Sarah Solomon, Eri Katsuyama, Vasileios C Kyttaris, Vaishali R Moulton, George C Tsokos

Journal of immunology (Baltimore, Md. : 1950) 200 ( 9 ) 3077 - 3086 2018.5

Language：English Publishing type：Research paper (scientific journal)

Cytotoxic function and cytokine profile of NK cells are compromised in patients with systemic lupus erythematosus (SLE). CD3ζ, an important molecule for NK cell activation, is downregulated in SLE T cells and contributes to their altered function. However, little is known about the role of CD3ζ in SLE NK cells. We studied CD3ζ levels and its contribution to cytotoxic, degranulation, and cytokine production capacity of NK cells from patients with SLE. Furthermore, we studied the human NK cell line, NKL, in which manipulation of CD3ζ levels was achieved using small interfering RNA and NK cells from Rag2 mice deficient in CD3ζ. We found reduced CD3ζ expression in NK cells from SLE patients independent of disease activity. Downregulation of CD3ζ expression in NK cells is mediated, at least in part, by Caspase 3, the activity of which is higher in NK cells from patients with SLE compared with NK cells from healthy donors. CD3ζ levels correlated inversely with natural cytotoxicity and the percentage of cells capable of producing the proinflammatory cytokines IFN-γ and TNF. In contrast, CD3ζ levels showed a direct correlation with levels of Ab-dependent cellular cytotoxicity. Experiments performed in CD3ζ-silenced NKL and CD3ζ-deficient NK cells from Rag2 mice confirmed the dependence of NK cell function on CD3ζ levels. Our results demonstrate a differential role for CD3ζ in natural cytotoxicity and Ab-dependent cellular cytotoxicity. We conclude that downregulated CD3ζ confers a proinflammatory phenotype to SLE NK cells and contributes to their altered function in patients with SLE.

DOI： 10.4049/jimmunol.1700588

Anti-SS-A/Ro antibody positivity as a risk factor for relapse in patients with polymyositis/dermatomyositis. International journal

Noriko Tatebe, Ken-Ei Sada, Yosuke Asano, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Mariko Narazaki, Katsue Watanabe, Tomoko Kawabata, Jun Wada

Modern rheumatology 28 ( 1 ) 141 - 146 2018.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The objective of this study is to elucidate predictors of relapse in patients with polymyositis and dermatomyositis (PM/DM). METHODS: Fifty PM/DM patients who achieved disease stabilization at Okayama University Hospital in 2004-2014 were enrolled retrospectively. Candidate predictors such as demographic factors, clinical symptoms, laboratory data, and treatment status were compared. RESULTS: The mean age of enrolled patients was 58 years; 34 were female. The patient groupings were as follows: 21 with PM, 27 with DM, and two with clinically amyopathic DM. During a mean observation period of 685 d, 5 patients (10%) died and 20 (40%) relapsed. The relapsed patients displayed baseline muscle weakness less frequently (85% versus 100%, p = .03) and anti-SS-A/Ro antibody more frequently (65% versus 27%, p = .007). Anti-SS-A/Ro-positive patients exhibited a higher relapse rate than anti-SS-A/Ro-negative patients (log-rank test, p = .03). Anti-SS-A/Ro-positive patients also exhibited higher anti-Jo-1 antibody positivity and lower levels of serum complement. After adjusting anti-Jo-1 antibody positivity, age, sex, CK <500 IU/L, and lung involvement, anti-SS-A/Ro positivity was still an independent risk factor for higher relapse-rate (odds ratio, 5.5; 95% confidence interval, 1.4-25.1). CONCLUSIONS: Anti-SS-A/Ro antibody positivity may be a useful biomarker for prediction of relapse.

DOI： 10.1080/14397595.2017.1317377

【炎症・免疫疾患とmicroRNA】miR-200a-3pによるSLEモデルマウスのT細胞のIL-2の産生制御機構

勝山惠理, 渡部克枝, 和田淳

臨床免疫・アレルギー科 69 ( 1 ) 40 - 45 2018.1

Central Diabetes Insipidus in Refractory Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Ken-Ei Sada, Takayuki Katsuyama, Yoshia Miyawaki, Eri Katsuyama, Mariko Narazaki, Noriko Tatebe, Katsue Watanabe, Tomoko Kawabata, Jun Wada

Internal medicine (Tokyo, Japan) 56 ( 21 ) 2943 - 2948 2017.11

Language：English Publishing type：Research paper (scientific journal)

We herein describe two cases of refractory antineutrophil cytoplasmic antibody-associated vasculitis (AAV) complicated with diabetes insipidus (DI) possibly related to hypertrophic pachymeningitis (HP). One patient had microscopic polyangiitis and HP, which were refractory to cyclophosphamide, azathioprine, rituximab, mycophenolate mofetil (MMF), and mizoribine. Remission was finally achieved with the use of etanercept, but DI occurred 5 years later. The other patient had granulomatosis with polyangiitis, which that was refractory to cyclophosphamide, methotrexate, MMF, and rituximab. DI subsequently developed, but was successfully treated with etanercept. Dura mater hypertrophy was macroscopically observed in the latter case.

DOI： 10.2169/internalmedicine.8683-16

Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who Was Unable to Continue Anti-TNF Therapy.

Eri Katsuyama, Hiroshi Wakabayashi, Ken-Ei Sada, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Mariko Narazaki, Noriko Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Jun Wada

Acta medica Okayama 71 ( 5 ) 445 - 448 2017.10

Language：English Publishing type：Research paper (scientific journal)

We herein present a case of a 38-year-old man who had bamboo spine and severe sacroiliitis and who was diagnosed with ankylosing spondylitis (AS). Infliximab (IFX) markedly improved the axial symptom but was discontinued due to the side effect of peripheral neuropathy. Switching from IFX to etanercept worsened the side effect. Rituximab (RTX) administration elicited a good response without side effects. RTX might be a suitable option for AS therapy when TNF inhibitors are difficult to use.

DOI： 10.18926/AMO/55444

Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice. International journal

Haruki Watanabe, Katsue S Watanabe, Keyue Liu, Sumie Hiramatsu, Sonia Zeggar, Eri Katsuyama, Noriko Tatebe, Akiya Akahoshi, Fumiaki Takenaka, Takahisa Hanada, Masaru Akehi, Takanori Sasaki, Ken-Ei Sada, Eiji Matsuura, Masahiro Nishibori, Jun Wada

Molecular therapy. Methods & clinical development 6 31 - 39 2017.9

Language：English Publishing type：Research paper (scientific journal)

We evaluated the efficacy of a neutralizing anti-high mobility group box 1 (HMGB1) monoclonal antibody in MRL/lpr lupus-prone mice. The anti-HMGB1 monoclonal antibody (5 mg/kg weight) or class-matched control immunoglobulin G2a (IgG2a) was administered intravenously twice a week for 4-15 weeks. Urine albumin was monitored, and histological evaluation of the kidneys was conducted at 16 weeks. Lymphadenopathies were evaluated by 1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl)cytosine ([18F]FAC) positron emission tomography/computed tomography (PET/CT) at 12 weeks. Following 4-week treatment, [18F]FAC-PET/CT showed similar accumulation in cervical and axillary lymph nodes at 12 weeks of age. However, anti-HMGB1 monoclonal antibody sufficiently inhibited the increase in albuminuria compared to an isotype control following 15-week treatment. Complement deposition was also improved; however, there were no significant differences in IgG deposition and renal pathological scores between the two groups. Anti-double-stranded DNA (dsDNA) antibody titers and cytokine and chemokine levels were also unaltered. Although there were no significant differences in glomerular macrophage infiltration, neutrophil infiltration was significantly decreased by the anti-HMGB1 monoclonal antibody. Antagonizing HMGB1 treatment suppressed HMGB1 translocation from nuclei in the kidney and suppressed neutrophil extracellular traps. The anti-HMGB1 monoclonal antibody demonstrated therapeutic potential against albuminuria in lupus nephritis by inhibiting neutrophil recruitment and neutrophil extracellular traps.

DOI： 10.1016/j.omtm.2017.05.006

Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents. International journal

Takayuki Katsuyama, Ken-Ei Sada, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Eri Katsuyama, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Kohei Miyake, Toru Kiguchi, Jun Wada

Modern rheumatology 27 ( 5 ) 773 - 777 2017.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. METHODS: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. RESULTS: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein-Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. CONCLUSIONS: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.

DOI： 10.1080/14397595.2016.1259714

Downregulation of miR-200a-3p, Targeting CtBP2 Complex, Is Involved in the Hypoproduction of IL-2 in Systemic Lupus Erythematosus-Derived T Cells. International journal

Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Mariko Narazaki, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R Moulton, George C Tsokos, Ken-Ei Sada, Jun Wada

Journal of immunology (Baltimore, Md. : 1950) 198 ( 11 ) 4268 - 4276 2017.6

Language：English Publishing type：Research paper (scientific journal)

Systemic lupus erythematosus (SLE) damages multiple organs by producing various autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and C-terminal binding protein 2 (CtBP2) in a lupus-prone mouse. First, we performed RNA sequencing to identify candidate microRNAs and mRNAs involved in the pathogenesis of SLE. We found that miR-200a-3p was significantly downregulated, whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4+ T cells from MRL/lpr-Tnfrsf6lpr mice compared with C57BL/6J mice. ZEB1 and ZEB2 comprise the ZEB family and suppress various genes, including IL-2 by recruiting CtBP2. IL-2 plays a critical role in immune tolerance, and insufficient IL-2 production upon stimulation has been recognized in SLE pathogenesis. Therefore, we hypothesized that decreased miR-200a-3p causes IL-2 deficit through the ZEB1-CtBP2 and/or ZEB2-CtBP2 complex in SLE CD4+ T cells. Overexpression of miR-200a-3p induced IL-2 production by downregulating ZEB1, ZEB2, and CtBP2 in EL4 cell lines. We further revealed that miR-200a-3p promotes IL-2 expression by reducing the binding of suppressive ZEB1-CtBP2 and ZEB2-CtBP2 complexes on negative regulatory element A in the IL-2 promoter in EL4 cells. Interestingly, the ZEB1-CtBP2 complex on negative regulatory element A was significantly upregulated after PMA/ionomycin stimulation in lupus CD4+ T cells. Our studies have revealed a new epigenetic pathway in the control of IL-2 production in SLE whereby low levels of miR-200a-3p accumulate the binding of the ZEB1-CtBP2 complex to the IL-2 promoter and suppress IL-2 production.

DOI： 10.4049/jimmunol.1601705

Azathioprine Intolerance in Japanese Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Michiko Morishita, Haruki Watanabe, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano Narazaki, Noriko Toyota Tatebe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

Internal medicine (Tokyo, Japan) 56 ( 13 ) 1645 - 1650 2017

Language：English Publishing type：Research paper (scientific journal)

Objective To assess the safety of azathioprine (AZA) in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods We retrospectively enrolled 67 consecutive AAV patients who had initiated AZA treatment from January 2006 to August 2014 at Okayama University Hospital. We evaluated the development of severe adverse events (AEs), AZA discontinuation due to total AEs (severe AEs included) within 1 year, and AZA-associated risk factors. Results The patients' median age was 70 years old. Forty-nine women and 18 men participated at the initiation of the study. Fifty-eight (87%) patients experienced AEs, and 36 experienced severe AEs (21 hepatic and 11 cytopenic severe AEs). Thirty-one (46%) patients discontinued treatment because of AEs. Abnormal hepatic laboratory test results at the treatment initiation were more frequent in patients with hepatic severe AEs and were associated with treatment discontinuation. The leukocyte and neutrophil counts at the treatment initiation were lower in the patients who discontinued treatment because of cytopenic AEs than in those who continued treatment. Only two patients experienced flare-ups during treatment. Conclusion The AE-associated AZA discontinuation rate in Japanese AAV patients was relatively high. AZA use warrants caution in patients with abnormal hepatic laboratory test results or low leukocyte or neutrophil counts.

DOI： 10.2169/internalmedicine.56.8287

Azathioprine intolerance in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis

Michiko Morishita, Haruki Watanabe, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Keiji Ohashi, Yoshia Miyawaki, Eri Katsuyama, Takayuki Katsuyama, Mariko Takano Narazaki, Noriko Toyota Tatebe, Katsue Sunahori Watanabe, Tomoko Kawabata, Ken Ei Sada, Jun Wada

Internal Medicine 56 ( 13 ) 1645 - 1650 2017

Publishing type：Research paper (scientific journal)

© 2017 The Japanese Society of Internal Medicine. Objective To assess the safety of azathioprine (AZA) in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods We retrospectively enrolled 67 consecutive AAV patients who had initiated AZA treatment from January 2006 to August 2014 at Okayama University Hospital. We evaluated the development of severe adverse events (AEs), AZA discontinuation due to total AEs (severe AEs included) within 1 year, and AZA-associated risk factors. Results The patients’ median age was 70 years old. Forty-nine women and 18 men participated at the initiation of the study. Fifty-eight (87%) patients experienced AEs, and 36 experienced severe AEs (21 hepatic and 11 cytopenic severe AEs). Thirty-one (46%) patients discontinued treatment because of AEs. Abnormal hepatic laboratory test results at the treatment initiation were more frequent in patients with hepatic severe AEs and were associated with treatment discontinuation. The leukocyte and neutrophil counts at the treatment initiation were lower in the patients who discontinued treatment because of cytopenic AEs than in those who continued treatment. Only two patients experienced flare-ups during treatment. Conclusion The AE-associated AZA discontinuation rate in Japanese AAV patients was relatively high. AZA use warrants caution in patients with abnormal hepatic laboratory test results or low leukocyte or neutrophil counts.

DOI： 10.2169/internalmedicine.56.8287

A retrospective observational study of glucocorticoid-induced diabetes mellitus with IgA nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy. International journal

Yoshia Miyawaki, Takayuki Katsuyama, Ken-Ei Sada, Sumie Hiramatsu, Keiji Ohashi, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Tatsuyuki Inoue, Masaru Kinomura, Hitoshi Sugiyama, Jun Wada

PloS one 12 ( 5 ) e0178018 2017

Language：English Publishing type：Research paper (scientific journal)

AIMS: To evaluate the incidence of GC-DM among patients with immunoglobulin A nephropathy (IgAN) and to confirm the risk factors for the development of GC-DM. METHODS: The medical records of patients with IgAN newly treated with the protocol of tonsillectomy combined with steroid pulse therapy were reviewed. The primary outcome was the development of GC-DM within the hospitalization period and during one year of follow-up. RESULTS: During hospitalization, 19 of the 95 patients developed GC-DM (20.0%), and the patients with GC-DM were significantly older and had a higher rate of family history of diabetes and higher HbA1c levels. The prevalence of hypertension was higher and the eGFR was numerically lower in patients with GC-DM than in those without. Older age (≥45 years) and a family history of diabetes emerged as independent risk factors for the development of GC-DM (odds ratio [OR], 6.3 and 95% confidence interval [CI], 1.6-27.6; OR, 4.4 and 95% CI, 1.2-16.6, respectively). No patients were newly diagnosed with GC-DM during 1-year observation period at out-patient clinic. CONCLUSIONS: Among the patients with IgAN, 20% developed GC-DM during the hospitalization period, confirming the family history of diabetes is clinically necessary before starting GC therapy.

DOI： 10.1371/journal.pone.0178018

多発性筋炎・皮膚筋炎抗SS-A抗体は多発性筋炎/皮膚筋炎における再燃危険因子である Reviewed

建部智子, 佐田憲映, 浅野洋介, 平松澄恵, 宮脇義亜, 森下美智子, 大橋敬司, 渡辺晴樹, 勝山隆行, 勝山恵理, 楢崎真理子, 渡部克枝, 杉山晃一, 若林宏, 川畑智子, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 60回 453 - 453 2016.3

脊椎関節炎、その他リナグリプチンの予防内服によるステロイド糖尿病の発症抑制効果に関するパイロット研究

宮脇義亜, 佐田憲映, 平松澄恵, 大橋敬司, 森下美智子, 勝山隆行, 勝山恵理, 渡辺晴樹, 楢崎真理子, 建部智子, 渡部克枝, 川畑智子, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 60回 401 - 401 2016.3

The efficacy of add-on tacrolimus for minor flare in patients with systemic lupus erythematosus: a retrospective study

H. Watanabe, R. Yamanaka, KE Sada, S. Zeggar, E. Katsuyama, T. Katsuyama, M. T. Narazaki, N. T. Tatebe, K. Sugiyama, K. S. Watanabe, H. Wakabayashi, T. Kawabata, J. Wada, H. Makino

LUPUS 25 ( 1 ) 54 - 60 2016.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS LTD

Objective We have assessed the effectiveness of tacrolimus for minor flares in systemic lupus erythematosus (SLE) patients.
Methods The medical records of 313 patients were retrospectively reviewed over a period of seven years, from 2006 to 2013. We enrolled patients with minor flare treated with add-on tacrolimus, without glucocorticoid (GC) intensification (tacrolimus group). Minor flare was defined as a 1-point increase in a total score between 3 and 11 in the SLE Disease Activity Index (SLEDAI). We enrolled as controls patients who were administered increased doses of GC for minor flare (GC group). All patients were followed for one year. The primary outcome measure was the proportion of responders.
Results There were 14 eligible patients in the tacrolimus group and 20 eligible patients in the GC group. The mean SLEDAI at flare tended to be higher in the tacrolimus group than in the GC group (7.5 vs. 6.2, p=0.085). A mean dose of 1.6mg tacrolimus/day was administered for flare, while the mean GC dose was 13.7mg/day in the GC group. The proportion of responders was 86% (12/14) in the tacrolimus group and 75% (15/20) in the GC group (p=0.67). The mean dose of GC at 12 months was higher in the GC group than in the tacrolimus group (9.7mg/day vs. 7.1mg/day, p<0.05). Only one patient discontinued tacrolimus because of fatigue after three months.
Conclusion Adding tacrolimus without increasing the GC dose may provide an effective treatment option for minor flares in patients with SLE.

DOI： 10.1177/0961203315600538

Bilateral Abducens Nerve Palsy due to Idiopathic Intracranial Hypertension as an Initial Manifestation of Systemic Lupus Erythematosus.

Eri Katsuyama, Ken-Ei Sada, Noriko Tatebe, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Koichi Sugiyama, Katsue S Watanabe, Hiroshi Wakabayashi, Tomoko Kawabata, Jun Wada, Hirofumi Makino

Internal medicine (Tokyo, Japan) 55 ( 8 ) 991 - 4 2016

Language：English Publishing type：Research paper (scientific journal)

Idiopathic intracranial hypertension (IIH) is a syndrome of increased intracranial pressure and presents as an intractable headache, vomiting, and ophthalmologic manifestations. We herein report the case of a young girl who presented with bilateral abducens nerve palsy due to IIH as the onset of systemic lupus erythematosus (SLE). The patient was successfully treated with corticosteroid therapy. Our case lacked the typical symptoms of IIH, such as headache or nausea; therefore, it is necessary to carefully determine the cause of bilateral abducens nerve palsies. The development of IIH in SLE patients is a rare occurrence, but this manifestation should not be overlooked.

DOI： 10.2169/internalmedicine.55.5990

Risk factors for the development of glucocorticoid-induced diabetes mellitus. International journal

Takayuki Katsuyama, Ken-Ei Sada, Sayaka Namba, Haruki Watanabe, Eri Katsuyama, Toshio Yamanari, Jun Wada, Hirofumi Makino

Diabetes research and clinical practice 108 ( 2 ) 273 - 9 2015.5

Language：English Publishing type：Research paper (scientific journal)

AIMS: To evaluate the incidence of glucocorticoid-induced diabetes mellitus (GC-DM) by repeated measurements of the postprandial glucose and detect predictors for the development of GC-DM. METHODS: Inpatients with rheumatic or renal disease who received glucocorticoid therapy were enrolled in this study. We compared the clinical and laboratory parameters of the GC-DM group with the non-GC-DM group and performed a multivariate analysis to identify risk factors. RESULTS: During a four-week period, 84 of the 128 patients (65.6%) developed GC-DM. All patients were diagnosed based on the detection of postprandial hyperglycemia. The GC-DM group had an older age (65.2 vs. 50.4 years, p<0.0001), higher levels of fasting plasma glucose (93.3 vs. 89.0mg/dl, p=0.027) and HbA1c (5.78 vs. 5.50%, 39.7 vs. 36.6 mmol/mol, p=0.001) and lower eGFR values (54.0 vs. 77.1 ml/min/1.73 m(2), p=0.0003) than the non-GC-DM group. According to the multivariate analysis, an older age (more than or equal to 65 years), higher HbA1c level (more than or equal to 6.0%) and lower eGFR (<40 ml/min/1.73m(2)) were identified as independent risk factors for GC-DM (OR 2.95, 95% CI 1.15-7.92, OR: 3.05, 95% CI 1.11-9.21, OR: 3.42, 95% CI: 1.22-10.8, respectively). The risk ratio for the development of GC-DM in the patients with at least one of these three risk factors was 2.28. The dose of glucocorticoids was not statistically related to the development of GC-DM. CONCLUSIONS: Patients with an older age, higher HbA1c level and lower eGFR require close monitoring for the development of GC-DM, regardless of the dose of glucocorticoids being administered.

DOI： 10.1016/j.diabres.2015.02.010

顕微鏡的多発血管炎による脳出血で死亡に至った1剖検例

宮脇義亜, 佐田憲映, 大橋敬司, 森下美智子, 勝山隆行, 勝山恵理, 渡辺晴樹, 楢崎真理子, 建部智子, 杉山晃一, 渡部克枝, 若林宏, 川畑智子, 和田淳, 槇野博史

日本リウマチ学会総会・学術集会プログラム・抄録集 59回 587 - 587 2015.3

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