九州大学-研究者情報 [木本泰孝 (助教) 九州大学病院免疫・膠原病・感染症内科]

木本泰孝（きもとやすたか）

データ更新日：2024.04.09

助教　／　九州大学病院免疫・膠原病・感染症内科

原著論文

1.	Yusuke Kashiwado, Yasutaka Kimoto, Kenji Oku, Mari Yamamoto, Shiro Ohshima, Satoshi Ito, Takahiko Horiuchi, Tsutomu Takeuchi, Prognostic improvement and treatment of COVID-19 in patients with rheumatic diseases until December 2022: Analysis of the JCR COVID-19 registry in Japan, Mod Rheumatol, 10.1093/mr/road057, 34, 3, 576-583, 2024.03.
2.	Fumiaki Sagawa, Hisakata Yamada, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Masakazu Kondo, Yasuharu Nakashima, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Determination of the factors associated with antigen-specific CD4+ T-cell responses to BNT162b2 in patients with rheumatoid arthritis, RMD Open, 10.1136/rmdopen-2023-003693., 10, 1, e003693, 2024.01.
3.	Nobuyuki Ono, Tatsuya Kai, Yukiko Takeyama, Yasushi Inoue, Naoyasu Ueda, Shuji Nagano, Shunichiro Ohta, Hisako Inoue, Takuya Sawabe, Yutaka Chifu, Seiji Yoshizawa, Kensuke Oryoji, Yasutaka Kimoto, Katsuhisa Miyake, Masahiro Ayano, Hiroki Mitoma, Yojiro Arinobu, Tomoya Miyamura, Takahiko Horiuchi, Koichi Akashi, Yoshifumi Tada, Hiroaki Niiro, Recent advances in the treatment strategy for AAV improved outcomes with intensive GC tapering, Int J Rheum Dis, 10.1111/1756-185X.15009., 27, 1, e15009, 2024.01.
4.	Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Safety and efficacy of switching immunosuppressive drugs for maintenance treatment in patients with systemic lupus erythematosus: A retrospective cohort study, Mod Rheumatol, 10.1093/mr/roac100., 33, 5, 961-967, 2023.08.
5.	Rioko Migita, Atsushi Tanaka, Kazuki Tanimoto, Junki Hiura, Yasutaka Kimoto, Takahiko Horiuchi, Yasushi Inoue, A case in which baricitinib was effective for both rheumatoid arthritis and essential thrombocythemia, Mod Rheumatol Case Rep, 10.1093/mrcr/rxad012., 8, 1, 1-4, 2023.12.
6.	Yusuke Kashiwado, Yasutaka Kimoto, Shiro Ohshima, Takuya Sawabe, Kensuke Irino, Shota Nakano, Junki Hiura, Akiko Yonekawa, Qiaolei Wang, Goro Doi, Masahiro Ayano, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Hiroaki Niiro, Taeko Hotta, Dongchon Kang, Nobuyuki Shimono, Koichi Akashi, Tsutomu Takeuchi, Takahiko Horiuchi, Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients, Rheumatology (Oxford) , 10.1093/rheumatology/kead275, 63, 3, 725-733, 2024.03.
7.	Kana Yokoyama, Hiroki Mitoma, Shotaro Kawano, Yusuke Yamauchi, Qiaolei Wang, Masahiro Ayano, Yasutaka Kimoto, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, CEACAM 1, 3, 5 and 6 -positive classical monocytes correlate with interstitial lung disease in early systemic sclerosis, Front Immunol, 10.3389/fimmu.2022.1016914., 13, 1016914, 2023.05.
8.	Yusuke Kashiwado, Yasutaka Kimoto, Takuya Sawabe, Kensuke Irino, Shota Nakano, Junki Hiura, Qiaolei Wang, Shotaro Kawano, Masahiro Ayano, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Hiroaki Niiro, Taeko Hotta, Dongchon Kang, Koichi Akashi, Shiro Ohshima, Tsutomu Takeuchi, Takahiko Horiuchi, Antibody Response to SARS-CoV-2 mRNA Vaccines in Patients with Rheumatic Diseases in Japan: Interim Analysis of a Multicenter Cohort Study., Mod Rheumatol, 10.1093/mr/roac030., 33, 2, 367-372, 2023.03.
9.	Fujimoto, Sho; Arinobu, Yojiro; Miyawaki, Kohta; Ayano, Masahiro; Mitoma, Hiroki; Kimoto, Yasutaka; Ono, Nobuyuki; Akashi, Koichi; Horiuchi, Takahiko; Niiro, Hiroaki, Anti-dsDNA IgE induces IL-4 production from basophils, potentially involved in B-cell differentiation in systemic lupus erythematosus, RHEUMATOLOGY, 10.1093/rheumatology/kead082, 2023.02.
10.	Kenji Oku, Yasutaka Kimoto, Takahiko Horiuchi, Mari Yamamoto, Yasushi Kondo, Masashi Okamoto, Tatsuya Atsumi, Tsutomu Takeuchi, Risk factors for hospitalization or mortality for COVID-19 in patients with rheumatic diseases: Results of a nation-wide JCR COVID-19 registry in Japan, Mod Rheumatol., 10.1093/mr/roac104., 33, 4, 768-766, 2023.07.
11.	Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Safety and efficacy of switching immunosuppressive drugs for maintenance treatment in patients with systemic lupus erythematosus: A retrospective cohort study, MODERN RHEUMATOLOGY, 10.1093/mr/roac100, 2022.08.
12.	Ayano, Masahiro; Kimoto, Yasutaka; Mitoma, Hiroki; Akahoshi, Mitsuteru; Ono, Nobuyuki; Arinobu, Yojiro; Akashi, Koichi; Horiuchi, Takahiko; Niiro, Hiroaki, Safety and efficacy of switching immunosuppressive drugs for maintenance treatment in patients with systemic lupus erythematosus: A retrospective cohort study, MODERN RHEUMATOLOGY, 10.1093/mr/roac100, 2022.08.
13.	Kimoto Y, Horiuchi T., The Complement System and ANCA Associated Vasculitis in the Era of Anti-Complement Drugs., Front Immunol, 10.3389/fimmu.2022.926044., 13, 926044, 2022.06.
14.	Yusuke Kashiwado, Chikako Kiyohara, Yasutaka Kimoto, Shuji Nagano, Takuya Sawabe, Kensuke Oryoji, Shinichi Mizuki, Hiroaki Nishizaka, Seiji Yoshizawa, Shigeru Yoshizawa, Tomomi Tsuru, Yasushi Inoue, Naoyasu Ueda, Shun-Ichiro Ota, Yasuo Suenaga, Tomoya Miyamura, Yoshifumi Tada, Hiroaki Niiro, Koichi Akashi, Takahiko Horiuchi, Clinical course of patients with rheumatoid arthritis who continue or discontinue biologic therapy after hospitalization for infection: a retrospective observational study, ARTHRITIS RESEARCH & THERAPY, 10.1186/s13075-022-02820-y, 24, 1, 131, 2022.06.
15.	Chihiro Saiki, Yusuke Kashiwado, Taku Yokoyama, Masahiro Ayano, Keisuke Imabayashi, Shotaro Kawano , Kazuhiko Higashioka, Yasutaka Kimoto, Mitsuhiro Fukata, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Successful transition from intravenous epoprostenol to oral selexipag and inhaled iloprost in a case of severe pulmonary arterial hypertension associated with systemic lupus erythematosus, Mod Rheumatol Case Rep, 10.1093/mrcr/rxac009., 6, 2, 138-188, 2022.06.
16.	Saiki C, Kashiwado Y, Yokoyama T, Ayano M, Imabayashi K, Kawano S, Higashioka K, Kimoto Y, Fukata M, Mitoma H, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H., Successful Transition from Intravenous Epoprostenol to Oral Selexipag and Inhaled Iloprost in a Case of Severe Pulmonary Arterial Hypertension Associated with Systemic Lupus Erythematosus. , Mod Rheumatol Case Rep. , 10.1093/mrcr/rxac009., 2022.05.
17.	Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Comparative efficacy and safety of mizoribine and mycophenolate mofetil for treating systemic lupus erythematosus: a retrospective cohort study, THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASE, 10.1177/1759720X221096367, 14, 2022.05.
18.	Kawano S, Mitoma H, Inokuchi S, Yamauchi Y, Yokoyama K, Nogami J, Semba Y, Ayano M, Kimoto Y, Akahoshi M, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H. , TNFR2 Signaling Enhances Suppressive Abilities of Human Circulating T Follicular Regulatory Cells, J Immunol., 10.4049/jimmunol.2100323., 208, 5, 1057-1065, 2022.03.
19.	Inokuchi S, Mitoma H, Kawano S, Ayano M, Kimoto Y, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niiro H., Activation of caspase-1 is mediated by stimulation of interferon genes and NLR family pyrin domain containing 3 in monocytes of active systemic lupus erythematosus, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 40, 3, 522-531, 2022.03.
20.	Shotaro Kawano, Hiroki Mitoma, Shoichiro Inokuchi, Yusuke Yamauchi, Kana Yokoyama, Jumpei Nogami, Yuichiro Semba, Masahiro Ayano, Yasutaka Kimoto, Mitsuteru Akahoshi, Nobuyuki Ono, Yojiro Arinobu, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, TNFR2 Signaling Enhances Suppressive Abilities of Human Circulating T Follicular Regulatory Cells, J Immunol, 10.4049/jimmunol.2100323., 208, 5, 1057-1065, 2022.03, T follicular regulatory (Tfr) cells are a subset of CD4+ T cells that express CXCR5 and migrate into germinal centers (GCs). They regulate GC reactions by communicating with T follicular helper (Tfh) and B cells. TNF inhibitors are used in inflammatory diseases; however, the generation of autoantibodies or anti-drug Abs sometimes causes problems. Because TNFR2 signaling is important for suppressive functions of regulatory T cells, we investigated the role of TNFR2 on human Tfr cells. Tfr cells stimulated with MR2-1 (an anti-TNFR2 agonistic Ab) were analyzed for cell proliferation, Foxp3 expression, and surface molecules. Tfh/B cell proliferation, IgM production, and differentiation in cocultures with MR2-1-stimulated Tfr cells were examined. Tfr cells express a high level of TNFR2. MR2-1 stimulation altered the gene expression profile of Tfr cells. Cell proliferation and Foxp3 expression of Tfr cells were enhanced by MR2-1. MR2-1-stimulated Tfr cells expressed ICOS and Programmed cell death protein 1 and significantly suppressed Tfh/B cell proliferation, IgM production, and B cell differentiation. TNFR2-stimulated Tfr cells retained the migration function according to the CXCL13 gradient. In conclusion, we showed that TNFR2-stiumulated Tfr cells can regulate Tfh and B cells. Aberrant antibody production during TNF inhibitor treatment might be, at least in part, associated with TNFR2 signaling inhibition in Tfr cells. In addition, expansion and maturation of Tfr cells via TNFR2 stimulation in vitro may be useful for a cell-based therapy in inflammatory and autoimmune diseases to control GC reactions..
21.	Rioko Migita, Yasutaka Kimoto, Junki Hiura, Yuta Okumura, Takahiko Horiuchi, A Case of Rapidly Progressing Hepatocellular Carcinoma after Administration of JAK Inhibitors to Treat Rheumatoid Arthritis., Case Rep Rheumatol, 10.1155/2022/6852189., 2022:6852189., 2022.03.
22.	Migita R, Kimoto Y, Hiura J, Okumura Y, Horiuchi T , A Case of Rapidly Progressing Hepatocellular Carcinoma after Administration of JAK Inhibitors to Treat Rheumatoid Arthritis., Case Rep Rheumatol, 10.1155/2022/6852189., 6852189, 2022.03.
23.	Ayano M, Kimoto Y, Mitoma H, Akahoshi M, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H., Hydroxychloroquine versus tacrolimus for the treatment of persistently active systemic lupus erythematosus, MODERN RHEUMATOLOGY, 10.1093/mr/roab010, 32, 2, 345-350, 2022.02.
24.	Kushimoto K, Ayano M, Nishimura K, Nakano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H., HLA-B52 allele in giant cell arteritis may indicate diffuse large-vessel vasculitis formation: a retrospective study, ARTHRITIS RESEARCH & THERAPY, 10.1186/s13075-021-02618-4, 23, 1, 2021.09.
25.	Irino K, Arinobu Y, Ayano M, Kawano S, Kimoto Y, Mitoma H, Akahoshi M, Akashi K, Horiuchi T, Niiro H., Predictive factors of fetal and maternal pregnancy outcomes in Japanese patients with systemic lupus erythematosus, LUPUS, 10.1177/09612033211031989, 30, 10, 1637-1643, 2021.09.
26.	Nakano M, Ayano M, Kushimoto K, Kawano S, Higashioka K, Inokuchi S, Mitoma H, Kimoto Y, Akahoshi M, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H., Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus, SCIENTIFIC REPORTS, 10.1038/s41598-021-95711-2, 11, 1, 2021.08.
27.	Imabayashi K, Ayano M, Higashioka K, Yokoyama K, Yamamoto K, Takayama K, Mitoma H, Kimoto Y, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niiro H., Infliximab for reversible dementia in acute onset of neuro-Behçet's disease: A case report and cytokine analysis, J Neuroimmunol., 10.1016/j.jneuroim.2021.577631., 357, 577631, 2021.08.
28.	Nakano M, Ayano M, Kushimoto K, Kawano S, Higashioka K, Inokuchi S, Mitoma H, Kimoto Y, Akahoshi M, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H, Increased Proportion of CD226(+) B Cells Is Associated With the Disease Activity and Prognosis of Systemic Lupus Erythematosus, FRONTIERS IN IMMUNOLOGY, 10.3389/fimmu.2021.713225, 12, 2021.07.
29.	Mishima K, Ayano M, Nishida T, Tatsutani T, Inokuchi S, Kimoto Y, Mitoma H, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niiro H. , Use of (18)F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography to successfully diagnose central nervous system vasculitis in systemic lupus erythematosus and antiphospholipid syndrome: a case report, Mod Rheumatol Case Rep. , 10.1080/24725625.2021.1905220., 5, 2, 278-284, 2021.07.
30.	Arinobu Y, Kashiwado Y, Miyawaki K, Ayano M, Kimoto Y, Mitoma H, Akahoshi M, Miyamoto T, Horiuchi T, Akashi K, Niiro H., Autoimmune manifestations associated with myelodysplastic syndrome predict a poor prognosis., Medicine (Baltimore) , 10.1097/MD.0000000000025406, 100, 13, e25406, 2021.04.
31.	Mishima K, Ayano M, Nishida T, Tatsutani T, Inokuchi S, Kimoto Y, Mitoma H, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niiro H., Use of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography to successfully diagnose central nervous system vasculitis in systemic lupus erythematosus and antiphospholipid syndrome: a case report., Mod Rheumatol Case Rep, 10.1080/24725625.2021.1905220., 2021.04.
32.	Higashioka K, Yoshimura M, Sakuragi T, Ayano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Kikukawa M, Yamada H, Horiuchi T, Akashi K, Niiro H., Human PD-1(hi)CD8(+) T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis, FRONTIERS IN IMMUNOLOGY, 10.3389/fimmu.2021.654623, 12, 2021.03.
33.	Inokuchi S, Mitoma H, Kawano S, Ayano M, Kimoto Y, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niiro H, Activation of caspase-1 is mediated by stimulation of interferon genes and NLR family pyrin domain containing 3 in monocytes of active systemic lupus erythematosus, Clin Exp Rheumatol, 2021.03.
34.	Akahoshi M, Arinobu Y, Kashiwado Y, Omoto A, Ayano M, Mitoma H, Kimoto Y, Ono N, Horiuchi T, Niiro H., IgG4-related disease presenting as a paraneoplastic syndrome: report of two cases and literature review., Mod Rheumatol Case Rep, 10.1080/24725625.2021.1896096., 2021.03.
35.	Nakayama T, Yoshimura M, Higashioka K, Miyawaki K, Ota Y, Ayano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Kikukawa M, Yamada H, Akashi K, Horiuchi T, Niiro H., Type 1 helper T cells generate CXCL9/10-producing T-bet(+) effector B cells potentially involved in the pathogenesis of rheumatoid arthritis, CELLULAR IMMUNOLOGY, 10.1016/j.cellimm.2020.104263, 360, 104263, 2021.02.
36.	Sasaki K, Tsuji T, Kimoto Y, Yanagihara Y, Masuguchi K, Chikamori A, Watanabe H, Murakami T, Oryoji D, Hashimoto M, Horiuchi T, Egashira N., Usefulness of daily folic acid supplementation during methotrexate treatment of Japanese patients with rheumatoid arthritis, MODERN RHEUMATOLOGY, 10.1080/14397595.2020.1743493, 31, 1, 108-113, 2021.01.
37.	Wang Q, Oryoji D, Mitoma H, Kimoto Y, Koyanagi M, Yokoyama K, Ayano M, Akahoshi M, Arinobu Y, Niiro H, Akashi K, Horiuchi T., Methotrexate Enhances Apoptosis of Transmembrane TNF-Expressing Cells Treated With Anti-TNF Agents, FRONTIERS IN IMMUNOLOGY, 10.3389/fimmu.2020.02042, 11, 2402, 2020.08.
38.	Ayano M, Arinobu Y, Tsukamoto H, Ota SI, Misaki K, Nishimura K, Kimoto Y, Mitoma H, Akahoshi M, Akashi K, Horiuchi T, Niiro H., Shoulder ultrasound and serum lactate dehydrogenase predict inadequate response to glucocorticoid treatment in patients with polymyalgia rheumatica, RHEUMATOLOGY INTERNATIONAL, 10.1007/s00296-020-04512-9, 40, 7, 1101-1109, 2020.07.
39.	Kazuhiko Higashioka, Yoshikane Kikushige, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Makoto Kikukawa, Mitsuteru Akahoshi, Yojiro Arinobu, Takahiko Horiuchi, Koichi Akashi, Hiroaki Niiro, Generation of a Novel CD30 + B Cell Subset Producing GM-CSF and Its Possible Link to the Pathogenesis of Systemic Sclerosis, Clin Exp Immunol, 10.1111/cei.13477, 2020.06.
40.	Yukiko Takeyama, Nobuyuki Ono, Yuri Shirahama, Yasushi Inoue, Atsushi Tanaka, Naoyasu Ueda, Naoya Nishimura, Shuji Nagano, Ayumi Uchino, Tomoya Miyamura, Kensuke Oryoji, Hisako Inoue, Akihito Maruyama, Shun-ichiro Ota, Seiji Yoshizawa, Takuya Sawabe, Naoko Himuro, Katsuhisa Miyake, Yasutaka Kimoto, Takahiko Horiuchi, Hiroki Mitoma, Hiroaki Niiro, Ayako Takamori, Yoshifumi Tada, Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan, Modern Rheumatology, 10.1080/14397595.2020.1790778, 2020.06, Objectives We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. Methods We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. Results We included 123 courses of 107 patients (RTX n = 14, IS n = 64, GC n = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (p = 0.122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. Conclusions RTX maintenance therapy could be effective and safe in Japanese GPA patients..
41.	Shoichiro Inokuchi, Hiroki Mitoma, Shotaro Kawano, Shota Nakano, Masahiro Ayano, Yasutaka Kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Hiroshi Tsukamoto, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Homeostatic milieu induces production of deoxyribonuclease 1-like 3 from myeloid cells, Journal of Immunology, 10.4049/jimmunol.1901304, 204, 8, 2088-2097, 2020.04, [URL], DNase 1-like 3 (DNase1L3), which belongs to DNase1 family, was originally identified as one of apoptosis- and necrosis-related endonucleases that fragmentate intranucleosomal DNA. A loss-of-function mutation has been reported in murine models of systemic lupus erythematosus (SLE) and in familial SLE patients. These reports suggest DNase1L3 plays an important role in the prevention of developing SLE; however, expression and function of DNase1L3 in human immune systems have been largely unclarified. As previous reports showed DNase1L3 is expressed in hematopoietic organs, we first analyzed expression levels of DNase1L3 in each subset of human peripheral blood cells by quantitative real-time PCR. Plasmacytoid dendritic cells showed the highest expression levels of DNase1L3 mRNA among peripheral blood cells. IL-4 enhanced DNase1L3 expression in monocytes, monocyte-derived dendritic cells, and monocyte-derived macrophages (MDMs), but not in T cells, B cells, or plasmacytoid dendritic cells. Together with IL-4, all-trans retinoic acid and apoptotic cells efficiently upregulated expression of DNalse1L3 in MDMs. As a result of intracellular signaling analysis, Jak1-IRS2-ERK/PI3K pathway was essential for IL-4-induced DNase1L3 expression. IL-4-treated monocyte-derived dendritic cells and MDMs secreted active DNase1L3 protein that could degrade liposome-DNA complexes, which were resistant to DNase1. Our results indicate DNase1L3 is secreted by innate immune cells and may play a critical role in the tissue homeostasis and on prevention of developing autoimmunity by degrading self-DNA..
42.	Masahiro Ayano, Yojiro Arinobu, Hiroshi Tsukamoto, Shun ichiro Ota, Kenta Misaki, Keisuke Nishimura, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro, Shoulder ultrasound and serum lactate dehydrogenase predict inadequate response to glucocorticoid treatment in patients with polymyalgia rheumatica, Rheumatology International, 10.1007/s00296-020-04512-9, 40, 7, 1101-1109, 2020.01, [URL], We aimed to identify predictors of inadequate response to glucocorticoid (GC) treatment in patients with polymyalgia rheumatica (PMR). We retrospectively studied 32 patients as a derivation cohort and 24 patients as a validation cohort. The patients were divided into two groups according to the response to GC treatment: GC-responders and GC-inadequate responders (GC-IRs). We compared laboratory data and bilateral shoulder ultrasound findings between the groups. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff value of candidate predictors of treatment response; the predictors were examined using multivariate logistic analysis. Gray-scale ultrasound findings of long head of the biceps (LHB) tenosynovitis and subacromial/subdeltoid (SAD) bursitis were scored semiquantitatively (0–3). A total gray-scale score (TGSS) was calculated as the sum of the gray-scale scores. In the derivation cohort, serum lactate dehydrogenase (LDH) levels and TGSS were significantly higher in GC-IRs than in GC-responders. On ROC analysis, the cutoff values of serum LDH levels ≥ 175 IU/ml and TGSS ≥ 5 were found to be the candidate predictors. Multivariate logistic analysis revealed an independent association of both the predictors with inadequate response to GC treatment. In the validation cohort, patients with one or both predictors exhibited a higher incidence of inadequate response to GC treatment. These findings indicate that the severities of LHB tenosynovitis and SAD bursitis evaluated using ultrasound and serum LDH levels are independent predictors of inadequate response to GC treatment in patients with PMR. Treatment adjustment based on prediction model may allow precise treatment of patients with PMR..
43.	Keiichi Sasaki, Toshikazu Tsuji, Yasutaka Kimoto, Yuki Yanagihara, Ken Masuguchi, Ayako Chikamori, Hiroyuki Watanabe, Tesshin Murakami, Daisuke Oryoji, Masafumi Hashimoto, Takahiko Horiuchi, Nobuaki Egashira, Usefulness of daily folic acid supplementation during methotrexate treatment of Japanese patients with rheumatoid arthritis, Modern Rheumatology, 10.1080/14397595.2020.1743493, 2020.01, [URL], Objectives: We investigated the effect of daily folic acid supplementation on methotrexate (MTX) toxicity and efficacy in Japanese patients with rheumatoid arthritis (RA). Methods: We followed 19 patients treated with MTX who switched from taking weekly 5 mg folic acid supplementation (weekly regimen) to 1.25 mg daily (daily regimen). White blood cell (WBC) and platelet (PLT) counts, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were collected for 24 weeks following the change. Results: We observed no significant changes in WBC or PLT counts. AST and ALT levels, which had exceeded the upper limits of their normal ranges at the beginning of the study, were improved significantly at weeks 4 and 8, no subsequent deterioration in liver function was found. Further, no significant changes in ESR and CRP levels were observed. Conclusion: Our data indicate that supplementing 1.25 mg of folic acid daily rather than 5 mg weekly reduces toxicity caused by MTX without affecting its efficacy..
44.	Nobuyuki Ono, Yasushi Inoue, Tomoya Miyamura, Naoyasu Ueda, Shuji Nagano, Hisako Inoue, Kensuke Oryoji, Shun-Ichiro Ota, Takuya Sawabe, Seiji Yoshizawa, Yukiko Takeyama, Yuri Sadanaga, Ayako Takamori, Yasutaka Kimoto, Katsuhisa Miyake, Takahiko Horiuchi, Hitoshi Nakashima, Hiroaki Niiro, Yoshifumi Tada, The Association of Airway Comorbidities With the Clinical Phenotypes and Outcomes of ANCA-associated Vasculitis Patients, J Rheumatol, 10.3899/jrheum.190373, 2019.09.
45.	Ayako Takaki-Kuwahara, Yojiro Arinobu, Kohta Miyawaki, Hisakata Yamada, Hirofumi Tsuzuki, Kensuke Irino, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Mitsuteru Akahoshi, Hiroshi Tsukamoto, Takahiko Horiuchi, Hiroaki Niiro, Koichi Akashi, CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines, Arthritis Research and Therapy, 10.1186/s13075-019-1984-x, 21, 1, 2019.08, [URL], Background: Recent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA). Methods: In a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients. Results: In the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p
46.	Masahiro Ayano, Hiroshi Tsukamoto, Hiroki Mitoma, yasutaka kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Toshihiro Miyamoto, Takahiko Horiuchi, Hiroaki Niiro, Koji Nagafuji, Mine Harada, Koichi Akashi, CD34-selected versus unmanipulated autologous haematopoietic stem cell transplantation in the treatment of severe systemic sclerosis A post hoc analysis of a phase I/II clinical trial conducted in Japan, Arthritis Research and Therapy, 10.1186/s13075-019-1823-0, 21, 1, 2019.01, [URL], Background: The effectiveness of autologous haematopoietic stem cell transplantation (auto-HSCT) in treating severe systemic sclerosis (SSc) is established; however, the necessity of purified CD34+ cell grafts and the appropriate conditioning regimen remain unclear. This study aimed to compare the efficacy and safety of CD34-selected auto-HSCT with unmanipulated auto-HSCT to treat severe SSc. Methods: This study was a post hoc analysis of a phase I/II clinical trial conducted in Japan. Nineteen patients with severe SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilised with cyclophosphamide (4 g/m ² ) and filgrastim (10 μg/kg/day). Following PBSC collection by apheresis, CD34+ cells were immunologically selected in 11 patients. All patients were treated with high-dose cyclophosphamide (200 mg/kg) monotherapy as a conditioning regimen and received CD34-selected (n = 11) or unmanipulated auto-HSCT (n = 8). Changes in skin sclerosis and pulmonary function were assessed over an 8-year follow-up period. Differences in the changes, toxicity, progression-free survival (PFS) and overall survival were compared between patients who had received CD34-selected auto-HSCT and those who had received unmanipulated auto-HSCT. Results: Skin sclerosis progressively improved after transplantation over an 8-year follow-up period in both groups, and the improvement was significantly greater in the CD34-selected group than in the unmanipulated group. Forced vital capacity in the CD34-selected group continuously increased over 8 years, whereas in the unmanipulated group it returned to baseline 3 years after transplantation. Toxicity and viral infections, such as cytomegalovirus infection and herpes zoster, were more frequently found in the CD34-selected group than in the unmanipulated group. The frequency of severe adverse events, such as bacterial infections or organ toxicity, was similar between the two groups. No treatment-related deaths occurred in either treatment group. PFS of the CD34-selected group was greater than that of the unmanipulated group, and the 5-year PFS rates of the CD34-selected and unmanipulated group were 81.8% and 50% respectively. Conclusions: CD34-selected auto-HSCT may produce favourable effects on improvement of skin sclerosis and pulmonary function compared with unmanipulated auto-HSCT. Use of CD34-selected auto-HSCT with high-dose cyclophosphamide monotherapy as a conditioning regimen may offer an excellent benefit-to-risk balance..
47.	Motoki Yoshimura, Hiroki Mitoma, Yasutaka Kimoto, Daisuke Oryoji, Yukimi Otsuka, Qiaolei Wang, Shoichiro Inokuchi, Masahiro Ayano, Mitsuteru Akahoshi, Yojiro Arinobu, Hiroaki Niiro, Koichi Kusuhara, Takahiko Horiuchi, A Japanese case of TNF receptor-associated periodic syndrome (TRAPS) successfully treated by canakinumab, Modern Rheumatology Case Reports, 3, 1, 49-52, 2018.10.
48.	Ueda Sho, Akahoshi Mitsuteru, Takeda A, Inoue Yasushi, Omoto Aya, Ayano Msahiro, Kimoto Yasutaka, Mitoma Hiroki, Arinobu Yojiro, Niiro Hiroaki, Tsukamoto Hiroshi, Horiuchi Takahiko, Hikita SI, Fukuhara T, Ishibashi T, Sonoda KH, Akashi Koichi., Long-term efficacy of infliximab treatment and the predictors of treatment outcomes in patients with refractory uveitis associated with Behçet's disease., Europian Journal of Rheumatology, 10.5152/eurjrheum.2017.17068, 5, 1, 9-15, 2018.05, OBJECTIVE: To assess the long-term efficacy and safety of infliximab (IFX) treatment for refractory uveitis associated with Behçet's disease (BD) and to identify predictors of long-term IFX therapy outcomes. METHODS: We retrospectively studied 44 consecutive BD patients with uveitis who were started on IFX therapy and analyzed the efficacy and safety of IFX and the treatment continuation rate. To determine predictors of IFX responsiveness, we analyzed the clinical characteristics of the patients who received regular maintenance therapy and those who required treatment intensification. The serum cytokine levels prior to IFX were measured through the Bio-Plex human cytokine assays. RESULTS: IFX significantly reduced the frequency of ocular attacks and improved the visual acuity of patients with BD-related uveitis. However, approximately half of the patients required dose escalations, necessitating a shortening of the intervals between IFX infusions due to loss of efficacy during the 5-year treatment. The frequency of ocular attacks was significantly higher in patients with complete BD than in patients with incomplete BD. A multiplex cytokine analysis revealed that patients with BD-related uveitis exhibited increased serum IL-2, IL-6, IL-8, and MCP-1 levels. Moreover, among BD patients, the serum IL-2 and IL-6 levels were particularly high in those who maintained remission and received regular IFX treatments. CONCLUSION: We confirmed the long-term efficacy and tolerability of IFX in patients with BD-related uveitis. Our results indicate that complete BD may be less responsive to IFX and that the pretreatment serum cytokine profiles may be useful for predicting the long-term IFX therapy outcomes..
49.	Otsuka Y, Kiyohara C, Kashiwado Y, Sawabe T, Nagano S, Kimoto Y, Ayano M, Mitoma H, Akahoshi M, Arinobu Y, Niiro H, Akashi K, Horiuchi T, Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study, PLOS ONE, 10.1371/journal.pone.0196368, 13, 4, 2018.04.
50.	Yoshihiro Higuchi, yasutaka kimoto, Rika Tanoue, Tomotake Tokunou, Kenichiro Tomonari, Toyoki Maeda, Takahiko Horiuchi, Cardiac sarcoidosis concomitant with large-vessel aortitis detected by ¹⁸F-fluorodeoxyglucose positron emission tomography, Internal Medicine, 10.2169/internalmedicine.9652-17, 57, 11, 1601-1604, 2018.01, [URL], We herein report a case of concurrent cardiac sarcoidosis and large-vessel aortitis detected by¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and followed up during immunosuppressive therapy. After high-dose prednisolone administration (1 mg/kg), serial FDG-PET showed that almost all of the abnormal FDG uptake in the heart and extracardiac region, including the abdominal to bilateral iliac arteries, had been disappeared. During the tapering of prednisolone, additive methotrexate therapy was needed to treat the recurrence of cardiac sarcoidosis. FDG-PET is a useful tool for detecting cardiac sarcoidosis concomitant with large-vessel aortitis and monitoring the effectiveness of immunosuppressive therapy..
51.	Makio Furukawa, Chikako Kiyohara, Takahiko Horiuchi, Hiroshi Tsukamoto, Hiroki Mitoma, yasutaka kimoto, Ayumi Uchino, Misato Nakagawa, Kensuke Oryoji, Terufumi Shimoda, Koichi Akashi, Quality of life in Japanese female patients with systemic lupus erythematosus Evaluation using the Short Form 36 Health Survey, Modern Rheumatology, 10.3109/14397595.2015.1060668, 26, 2, 240-247, 2016.03, [URL], Objective. Aspects of health-related quality of life (HRQoL) are important for assessing perceived health status and treatment burden. We evaluated HRQoL using Short Form 36 Health Survey (SF-36) and factors associated with HRQoL. Methods. We collected basic and lifestyle-related, clinical, and treatment characteristics among 119 female Japanese patients with systemic lupus erythematosus (SLE). Odds ratios (ORs) and their 95% confidence intervals were assessed for associations between HRQoL and selected factors. Results. Irregularity of sleep was significantly associated with risk of lower role physical (RP) (OR = 8.27), vitality (VT) (OR = 8.45), and role emotional (OR = 10.7) domains. Compared with clerical work, non-clerical work was significantly associated with risk of lower RP (OR = 7.39), and unemployment was significantly associated with risk of lower VT (OR = 41.0). Daily soybean intake was associated with improved General Health or GH (OR = 0.17). Compared with Systemic Lupus Collaborative Clinics Damage Index (SDI) = 0, SDI > 2 was associated with risk of lower PF (OR = 7.88), RP (OR = 4.29), and bodily pain (OR = 3.06) domains. Conclusion. Reduced HRQoL was observed in our SLE patients. Interventions addressing sleep and work disturbances, as well as daily soybean consumption, could alter the HRQoL of SLE patients..
52.	合田英明, 平瀬伸尚, 東保太郎, 伊藤能清, 木本泰孝, 有田好之, 生山祥一郎, 堀内孝彦, 難治性の自己免疫性血小板減少症を伴ったCD5陽性びまん性大細胞型B細胞性リンパ腫の一例, 臨牀と研究, 92, 7, 944-948, 2015.07.
53.	Atsushi Tanaka, Hiroshi Tsukamoto, Hiroki Mitoma, Kiyohara C, Yasutaka Kimoto, Mitsuteru Akahoshi, Yojiro Arinobu, Hiroaki Niiro, Takahiko Horiuchi, koichi akashi, Serum progranulin levels are elevated in dermatomyositis patients with acute interstitial lung disease, predicting prognosis, ARTHRITIS RESEARCH & THERAPY, 10.1186/s13075-015-0547-z, 17, 27, 2015.02.
54.	Tsuyoshi Nakayama, Mitsuteru Akahoshi, Kensuke Irino, Yasutaka Kimoto, Yojiro Arinobu, Hiroaki Niiro, Hiroshi Tsukamoto, Takahiko Horiuchi, koichi akashi, Transient antiphospholipid syndrome associated with primary cytomegalovirus infection: a case report and literature review., Case Rep Rheumatol, 10.1155/2014/271548, 271548, 2014.12, Viral infection is known to induce transient autoimmunity in humans. Acute cytomegalovirus (CMV) infection is implicated in occasional thrombosis formation. We here, for the first time, report a 19-year-old female who had an acute CMV infection, leading to a deep venous thrombosis and a pulmonary embolism along with transient appearance of lupus anticoagulant. The pathological role of antiphospholipid antibodies in CMV-mediated thrombosis is discussed..
55.	Yasutaka Kimoto, Shigeru Yoshizawa, Hiroaki Niiro, Hiroshi Tsukamoto, Takahiko Horiuchi, Pleuritis clinically diagnosed as aspergillosis during the course of microscopic polyangiitis., Internal Medicine, 10.2169/internalmedicine.53.2168, 53, 24, 2821-2824, 2014.12.
56.	Makio Furukawa, Chikako Kiyohara, Takahiko Horiuchi, Hiroshi Tsukamoto, Hiroki Mitoma, yasutaka kimoto, Ayumi Uchino, Misato Nakagawa, Kensuke Oryoji, Terufumi Shimoda, Mine Harada, Koichi Akashi, Prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus, Modern Rheumatology, 10.1007/s10165-012-0735-5, 23, 4, 765-773, 2013.07, [URL], Objective: We examined the prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus (SLE). Methods: We performed lateral radiographs of the thoracic and lumbar spine and bone mineral density (BMD) measurements and collected demographic, lifestyle, clinical, and treatment characteristics of 52 SLE patients. Vertebral fractures were defined as a >20 % reduction of vertebral body height. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were computed to assess the strength of associations between vertebral fractures and selected factors among SLE patients. Results: At least one vertebral fracture was detected in 50 % of SLE patients. A history of previous bone fracture was significantly associated with an increased risk of vertebral fractures among SLE patients (adjusted OR = 14.8, 95 % CI = 1.62-134; P = 0.017). Daily use of tea or coffee was marginally associated with a decreased risk of vertebral fractures among SLE patients (adjusted OR = 0.11, 95 % CI = 0.01-1.01; P = 0.051). Conclusion: The high prevalence of vertebral fracture in SLE patients (50 %) indicates that we need to assess the lateral spine radiograph in more female Japanese SLE patients regardless of BMD and use of corticosteroids, although additional studies are warranted to confirm the findings suggested in this study..
57.	Furukawa M, Kiyohara C, Tsukamoto H, Mitoma H, Kimoto Y, Uchino A, Nakagawa M, Oryoji K, Shimoda T, Akashi K, Harada M, Horiuchi T, Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus, RHEUMATOLOGY INTERNATIONAL, 10.1007/s00296-009-1244-5, 31, 3, 365-376, 2011.03.
58.	yasutaka kimoto, Takahiko Horiuchi, Hiroshi Tsukamoto, Chikako Kiyohara, Hiroki Mitoma, Ayumi Uchino, Isao Furugo, Seiji Yoshizawa, Akira Ueda, Shinichi Harashima, Takuya Sawabe, Tomoko Tahira, Kenshi Hayashi, Shigeru Yoshizawa, Terufumi Shimoda, Koichi Akashi, Mine Harada, Association of killer cell immunoglobulin-like receptor 2DL5 with systemic lupus erythematosus and accompanying infections, Rheumatology, 10.1093/rheumatology/keq050, 49, 7, 1346-1353, 2010.04, [URL], Objective. Identification of the association of killer cell immunoglobulin-like receptor (KIR) genes with SLE and accompanying infections. Methods. Presence or absence of all 14 KIR genes was studied for association with SLE by case-control studies. A total of 417 SLE cases, 72 RA cases and 256 controls, all of Japanese descent, were enrolled. Results. The carrier frequency of KIR2DL5 was significantly decreased in SLE patients compared with healthy controls [39.3 vs 50.4%; odds ratio (OR) = 0.64; 95% CI 0.36, 0.92; P = 0.005). When the prevalence of severe infections was analysed in 184 SLE patients, whose medical records were available, KIR2DL5 carriers were at an increased risk of overall infection and viral infection (crude OR = 2.66; 95% CI 1.43, 4.92; P = 0.017 and crude OR = 2.31; 95% CI 1.15, 4.62; P = 0.017, respectively). After adjusting for methylprednisolone pulse and/or cyclophosphamide pulse therapy, KIR2DL5 carriers were at significantly greater risk of infectious events overall (adjusted OR = 2.45; 95% CI 1.24, 4.81; P = 0.0095). However, KIR2DL5 carriers were marginally associated with an increased risk of viral infectious events (adjusted OR = 2.03; 95% CI 0.94, 4.41; P = 0.0718). Conclusion. KIR2DL5 was significantly associated with a decreased risk of SLE as well as an increased risk of infectious events overall in SLE patients. Our data suggest a further role of KIRs in the pathogenesis of autoimmune diseases and infection..
59.	Y. Tamimoto, Takahiko Horiuchi, H. Tsukamoto, J. Otsuka, Hiroki Mitoma, yasutaka kimoto, H. Nakashima, K. Muta, Y. Abe, Chikako Kiyohara, A. Ueda, K. Nagasawa, S. Yoshizawa, T. Shimoda, M. Harada, A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome Immunological analysis of B cells, T cells and cytokines, Rheumatology, 10.1093/rheumatology/ken071, 47, 6, 821-827, 2008.06, [URL], Objective. Accumulating evidence suggests that B-cell depletion therapy by rituximab may be effective for autoimmune disorders. However, an optimal dose of rituximab and a mechanism of its action remain to be established. We performed a dose-escalation study for treatment of Japanese patients with autoimmune diseases including eight with SLE and one with Evans' syndrome. Methods. Rituximab was infused intravenously, weekly 4 times in a dose-escalating fashion at three different doses of 100, 250 or 375 mg/m ² to three patients each. Immunological parameters were monitored at certain points until 12 months after the treatment. Results. Rituximab was well tolerated and safe in these patients. Seven out of eight SLE patients and one with Evans' syndrome clinically responded completely or partially to the treatment. Four patients achieved long-term remission (18-30 months) without any additional treatment. In these patients, a significant decrease in circulating B cells continued for 6 months after the treatment. The mean fluorescence intensities of CD19, CD21, CD40 and BR3 on the residual B cells as well as the percentage of CD69+ CD4+ T cells decreased significantly. Serum TNF-α levels decreased significantly on day 2. The Th1/Th2 balance of CD4+ T cells gradually shifted towards a Th1 type by 6 months. Conclusion. In addition to B-cell depletion, modification of B-cell and T-cell phenotypes as well as cytokine profiles may be involved in the action of rituximab..
60.	Hiroki Mitoma, Takahiko Horiuchi, Hiroshi Tsukamoto, Yasuhiro Tamimoto, yasutaka kimoto, Ayumi Uchino, Kentaro To, Shin Ichi Harashima, Nobuaki Hatta, Mine Harada, Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor α-expressing cells Comparison among infliximab, etanercept, and adalimumab, Arthritis and Rheumatism, 10.1002/art.23447, 58, 5, 1248-1257, 2008.05, [URL], Objective. Three anti-tumor necrosis factor α (anti-TNFα) agents have been proved to be effective for rheumatoid arthritis (RA) and other inflammatory disorders. Infliximab and adalimumab have been generated as anti-TNFα monoclonal antibodies, while etanercept is engineered from human type II TNF receptors. In spite of all 3 agents' equal efficacy for RA, both infliximab and adalimumab are effective for other diseases such as Crohn's disease and Wegener's granulomatosis, while etanercept is not. We undertook this study to understand the different clinical effects of these anti-TNFα agents by analyzing their biologic activities on transmembrane TNFα. Methods. Jurkat T cells stably expressing an uncleavable form of transmembrane TNFα were used for the following studies: 1) flow cytometric analysis of binding activities of anti-TNF agents to cell surface transmembrane TNFα, 2) complement-dependent cytotoxicity (CDC), 3) antibody-dependent cell-mediated cytotoxicity (ADCC) by using peripheral blood mononuclear cells, and 4) outside-to-inside (reverse) signal transduction through transmembrane TNFα estimated by apoptosis and cell cycle analysis using flow cytometry. Results. All of the anti-TNFα agents bound to transmembrane TNFα. Infliximab and adalimumab exerted almost equal CDC activities, while etanercept showed considerably lower activity. ADCC activities were almost equal among these 3 agents. Adalimumab and infliximab induced apoptosis and cell cycle arrest in transmembrane TNFα-expressing Jurkat T cells, reflecting an outside-to-inside signal transduction through transmembrane TNFα. Conclusion. Three different anti-TNF agents showed different biologic effects on transmembrane TNFα. This finding suggests that CDC and outside-to-inside signals by anti-TNFα antibodies may explain the successful clinical efficacy of adalimumab and infliximab in Crohn's disease and Wegener's granulomatosis..
61.	Horiuchi Miyagawa, M. Yamai, D. Sakaguchi, Chikako Kiyohara, H. Tsukamoto, yasutaka kimoto, T. Nakamura, J. H. Lee, C. Y. Tsai, B. L. Chiang, T. Shimoda, M. Harada, T. Tahira, K. Hayashi, Takahiko Horiuchi, Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus, Rheumatology, 10.1093/rheumatology/kem321, 47, 2, 158-164, 2008.02, [URL], Objective. Identification of the genes responsible for systemic lupus erythematosus (SLE). Methods. All the exons and putative promoter regions of 53 candidate genes (TNFRSF6/Fas, TNFSF6/FasL, Fli1, TNFSF10/TRAIL, TNFSF12/TWEAK, Bcl-2, PTEN, FADD, TRADD, CDKN1A, TNFRSF1A/TNFR1, TNFRSF4/OX40, TNFSF4/OX40L, TNFSF5/CD40L, TNFSF13B/BAFF, ICOS, CTLA4, CD28, FYN, G2A, CR2, PTPRC/CD45, CD22, CD19, Lyn, PDCD1, PTPN6, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, CD3Z, DNASE1, APCS, MERTK, C3, C1QA, C1QB, C1QG, C2, MBL2, IGHM, IL-2, IL-4, IL-10, IFNG, TNFA, MAN2A1, TNFRSF11A/RANK, TNFRSF11B/OPG, TNFSF11/OPGL) were screened for single nucleotide polymorphisms (SNPs) and their association with SLE was assessed by case-control studies. A total of 509 cases and 964 controls of Japanese descent were enrolled. Results. A total of 316 SNPs was identified. When analysed in the Japanese population, the allele frequencies of T at rs7951 and G at rs2230201 of the C3 gene were 0.110 and 0.626, respectively, in SLE patients; significantly higher than the frequencies of 0.081 and 0.584, respectively, in controls [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.05-1.86, P = 0.016 and OR = 1.19, 95% CI = 1.01-1.41, P = 0.038, respectively]. The mean serum C3 level of carriers of the rs7951 T allele was significantly lower than that of non-carriers of the T allele in 87 SLE patients whose medical records were available (P = 0.0018). Conclusion. rs7951 T allele of the C3 gene was significantly associated with SLE, and decreased serum level of C3 seems to be correlated with this allele..
62.	Tao K, Fujii M, Tsukumo S, Maekawa Y, Kishihara K, Kimoto Y, Horiuchi T, Hisaeda H, Akira S, Kagami S, Yasutomo K., Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population, ANNALS OF THE RHEUMATIC DISEASES, 10.1136/ard.2006.065961, 66, 7, 905-909, 2007.07.
63.	Takahiko Horiuchi, Chikako Kiyohara, Hiroshi Tsukamoto, Takuya Sawabe, Isao Furugo, Seiji Yoshizawa, Akira Ueda, Yoshifumi Tada, Tadashi Nakamura, yasutaka kimoto, Hiroki Mitoma, Shinichi Harashima, Shigeru Yoshizawa, Terufumi Shimoda, Seiichi Okamura, Kohei Nagasawa, Mine Harada, A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus A case-control study and a meta-analysis, Annals of the Rheumatic Diseases, 10.1136/ard.2006.058917, 66, 3, 320-324, 2007.03, [URL], Objectives: To perform a case-control study of a functional M196R polymorphism of tumour necrosis factor receptor type 2 (TNF-RII) in a Japanese population and a meta-analysis of all published reports on the polymorphism to investigate the association of the M196R polymorphism of TNF-RII with systemic lupus erythematosus (SLE). Methods: The functional M196R polymorphism of TNF-RII was genotyped by using polymerase chain reaction combined with the subsequent single-strand conformation polymorphism (PCR-SSCP) analysis for screening, followed by nucleotide sequencing for confirmation. A total of 331 patients and 359 controls were subjected to a case-control study. A meta-analysis of the available case-control studies including all published data as well as our own data was performed to investigate the association of the functional M196R polymorphism of TNF-RII with SLE. Results: Our case-control study did not show any significant association of a functional M196R polymorphism of TNF-RII with SLE, although there was a trend towards association. A meta-analysis of seven case-control studies in eight different ethnic populations including our own showed that 196M/R and 196R/R genotypes combined was significantly associated with an increased risk of SLE (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.04 to 1.60; p = 0.02). Stratification by ethnicity showed a more significant association in Asians, including Japanese, Korean and Vietnamese (OR 1.40, 95% CI 1.10 to 1.78; p = 0.006). The effect of the 196R allele on SLE was not clear in Caucasians. Conclusions: The 196R allele of the functional M196R polymorphism of TNF-RII is a risk factor for SLE, especially in the Asian population..
64.	Tsukamoto H, Horiuchi T, Kokuba H, Nagae S, Nishizaka H, Sawabe T, Harashima S, Himeji D, Koyama T, Otsuka J, Mitoma H, Kimoto Y, Hashimura C, Kitano E, Kitamura H, Furue M, Harada M, Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2005.02.159, 330, 1, 298-304, 2005.04.
65.	Hiroki Mitoma, Takahiko Horiuchi, yasutaka kimoto, Hiroshi Tsukamoto, Ayumi Uchino, Yasuhiro Tamimoto, Yugo Miyagi, Mine Harada, Decreased expression of interleukin-21 receptor on peripheral B lymphocytes in systemic lupus erythematosus., International journal of molecular medicine, 16, 4, 609-615, 2005.01, Interleukin-21 (IL-21) is the most recent member of the common gamma-chain-dependent cytokine family. We studied the expression of the IL-21 receptor (IL-21R) on peripheral B lymphocytes in patients with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSjS), and healthy controls. Naive B lymphocytes expressed higher levels of IL-21R than memory B lymphocytes and plasmablasts, both in SLE patients and healthy controls. The proportion of IL-21R+ cells in the total peripheral B lymphocytes, as well as those in the respective B lymphocyte subsets, was significantly lower in SLE compared with those of pSjS or healthy controls (p=0.0002 and p

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