Mechanisms and potential therapy of autoimmune arthritis

• Project/Area Number: 19591153
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: University of Tsukuba
• Principal Investigator: MATSUMOTO Isao University of Tsukuba, 大学院・人間総合科学研究科, 准教授 (30343081)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: リウマチ学 / glucose-6-phosphate isomerase / 関節リウマチ / Th17 / IL-6 / 動物モデル / 生物学的製剤

Research Abstract

GPI誘導関節炎モデルをもちいて、生物学的製剤に対する治療効果がRAに近似しており、病因、および治療効果のメカニズムを探索する上で優れた動物モデルと考えられた。またIL-6はTH17を選択的に誘導することによりGPI誘導性関節炎の発症に重要な役割を果たしていることが明らかになり、抗原特異的CD4+細胞の増殖や自己抗体の産生誘導にも関わる可能性が示唆された。また、adoptive transferモデルではB細胞は抗体産生細胞として機能していると考えられ、B細胞以外の脾細胞が産生するTNFαやIL-6と協調して、自己抗体が関節炎を誘導している可能性が示唆された。

Research Products

• [Journal Article] Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis : contribution to severe gastrointestinal tract dysmotility (2009)
  • Author(s): Kawaguchi Y, Nakamura Y, Matsumoto I, Nishimagi E, Kamatani N, Satoh T, Kuwana M, Sumida T, Hara M.
  • Journal Title: Ann Rheum Dis. (in press)
  • Peer Reviewed
• [Journal Article] Mannose binding lection gene polymorphisms and the severity of chronic periodontitis (2009)
  • Author(s): Tsutsumi A, Kobayashi T, Ito S, Goto D, Matsumoto I, Yoshie H, Sumida T.
  • Journal Title: Jap. J. Clin. Immunol 32 Pages: 48-52
  • Peer Reviewed
• [Journal Article] Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show reduced or insufficient response to infliximab (2009)
  • Author(s): Horikoshi M, Ito S, Ishikawa M, Umeda N, Kondo Y, Tsuboi H, Hayashi T, Goto D, Matsumoto I, Sumida T.
  • Journal Title: Mod Rheumatol (in press)
  • NAID: 10025112788
  • Peer Reviewed
• [Journal Article] A new low-field extremity magnetic resonance imaging and proposed compact MRI score- Evaluation of anti-tumor necrosis factor biologics on rheumatoid arthritis (2009)
  • Author(s): Suzuki T, Ito S, Handa S, Kose K, Okamoto Y, Minami M, Hayashi T, Goto D, Matsumoto I, Sumida T.
  • Journal Title: Mod Rheumatol (in press)
  • NAID: 10025113342
  • Peer Reviewed
• [Journal Article] B cell play crucial role as antigen presenting cells and collaborationg with inflammatory cytokines in glucose-6-phoaphate isomerase-induced arthritis (2009)
  • Author(s): Tanaka-Watanabe Y, Matsumoto I, Iwanami K, Inoue A, Goto D, Ito S, Tsutsumi A, Sumida T.
  • Journal Title: Clin Exp Immunol 155 Pages: 285-294
  • Peer Reviewed
• [Journal Article] N. Replication of the Association between C8orf13-BLK Region and Systemic Lupus Erythematosus in a Japanese Population (2009)
  • Author(s): Ito I, Kawasaki A, Ito S, Hayashi T, Goto D, Matsumoto I, Tsutsumi A, Geoffrey Hom, Robert R. Graham, Takasaki Y, Hashimoto H, Ohashi J, Timothy W. Behrens, Sumida T, Tsuchiya N.
  • Journal Title: Arthritis Rheum. 60 Pages: 553-558
  • Peer Reviewed
• [Journal Article] Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility (2009)
  • Author(s): Kawaguchi Y
  • Journal Title: Ann Rheum Dis. 68 Pages: 710-714
  • Peer Reviewed
• [Journal Article] Replication of the Association between C8orf13-BLK Region and Systemic Lupus Erythematosus in a Japanese Population (2009)
  • Author(s): Ito I
  • Journal Title: Arthritis Rheum 60 Pages: 553-558
  • Peer Reviewed
• [Journal Article] Arthritogenic T cell epitope in glucose-6-phosphate isomerase (GPI)-induced arthritis (2008)
  • Author(s): Iwanami K, Matsumoto I, Tanaka Y, Inoue A, Goto D, Ito S, Tsutsumi A, Sumida T.
  • Journal Title: Arthritis Res Ther 10
  • Peer Reviewed
• [Journal Article] Anti-glucose-6-phosphate isomerase, anti-cyclic citrullinated peptide antibodies and HLA-DRB1 genotypes in Japanese patients with early rheumatoid arthritis (2008)
  • Author(s): Furuya T, Matsumoto I, Tsuchiya N, Hakoda M, Ichikawa N, Higami K, Nanke Y, Sumida T, Kamatani N, Kotake S.
  • Journal Title: Clin Exp Rheumatol 26 Pages: 918-921
  • Peer Reviewed
• [Journal Article] Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population : a case-control association study of STAT1-STAT4 region (2008)
  • Author(s): Kawasaki A, Ito I, Hikami K, Ohashi J, Hayashi T, Goto D, Matsumoto I, Ito S, Tsutsumi A, Koga M, Arinami T, Robert R Graham, Geoffrey Hom, Takasaki Y, Hashimoto H, Timothy W Behrens, Sumida T, Tsuchiya N.
  • Journal Title: Arthritis Res Ther 10
  • NAID: 120007138342
  • Peer Reviewed
• [Journal Article] Intravascular large B-cell lymphoma with acute abdomen as a presentingsymptom in a patient with systemic lupus erythematosus (2008)
  • Author(s): Ishii W, Ito S, Kondo Y, Tsuboi H, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T, Okoshi Y, Hasegawa Y, Kojima H, Sakashita S, Aita K, Noguchi M.
  • Journal Title: J Clin Oncol 26 Pages: 1553-1555
  • Peer Reviewed
• [Journal Article] Crucial role of IL-6/IL-17 cytokine axis in the induction of arthritis by glucose-6-phosphate-isomerase (2008)
  • Author(s): Iwanami K, Matsumoto I, Watanabe Y, Mihara M, Ohsugi Y, Mamura M, Goto D, Ito S, Tsutsumi A, Kishimoto T, Sumida T.
  • Journal Title: Arthritis Rheum 58 Pages: 754-763
  • Peer Reviewed
• [Journal Article] Therapeutic effects of antibodies to TNF alpha and IL-6 and CTLA-4 Ig in mice with glucose-6-phosphate isomerase-induced arthritis (2008)
  • Author(s): Matsumoto I, Zhang H, Yasukochi T, Iwanami K, Tanaka Y, Inoue A, Goto D, Ito S, Tsutsumi A, Sumida T.
  • Journal Title: Arthritis Res Ther 10
  • Peer Reviewed
• [Journal Article] Visfatin(pre-B cell colony-enhancing factor) gene expression in patients with rheumatoid arthritis (2008)
  • Author(s): Matsui H, Tsutsumi A, Sugihara M, Suzuki T, Iwanami K, Kohno M, Goto D, Matsumoto I, Ito S, Sumida T.
  • Journal Title: Ann Rheum Dis. 67 Pages: 571-572
  • Peer Reviewed
• [Journal Article] Use of Laser Microdissection in the Analysis of Renal-infiltrating T cells in MRL/lpr Mice (2008)
  • Author(s): Wang Y, Ito S, Chino Y, Iwanami K, Yasukochi T, Goto D, Matsumoto I, Hayashi T, Uchida K, Sumida T.
  • Journal Title: Mod Rheumatol 18 Pages: 385-393
  • NAID: 10021946996
  • Peer Reviewed
• [Journal Article] Invariant NKT cells produce IL-17 through IL-23-dependent and -independent pathways with potential modulation of Th17 response in collagen-induced arthritis (2008)
  • Author(s): Yoshiga Y, Goto D, Segawa S, Ohnishi Y, Matsumoto I, Ito S, Tsutsumi A, Taniguchi M, Sumida T.
  • Journal Title: Int J Mol Med. 22 Pages: 369-374
  • Peer Reviewed
• [Journal Article] Highprevalence of autoantibodies tomuscarinic-3 acetylcholine receptor inpatients with juvenile-onset Sjogren'ssyndrome (2008)
  • Author(s): Nakamura Y, Wakamatsu E, Matsumoto I, Tomiita M, Kohno Y, Mori M, Yokota S, Goto D, Ito S, Tsutsumi A, Sumida T.
  • Journal Title: Ann Rheum Dis. 67 Pages: 136-137
  • Peer Reviewed
• [Journal Article] Arthritogenic T cell epitope in glucose-6-phosphate isomerase (GPI)-induced arthritis. (2008)
  • Author(s): Iwanami K
  • Journal Title: Arthritis Res Ther. 10
  • Peer Reviewed
• [Journal Article] Crucial role of IL-6/IL-17 cytokine axis in the induction of arthritis by glucose-6-phosphate-isomerase. (2008)
  • Author(s): Iwanami K
  • Journal Title: Arthritis Rheum. 58 Pages: 754-763
  • Peer Reviewed
• [Journal Article] Visfatin(pre-B cell colony -enhancing factor)gene expression in patients with rheumatoid arthritis. (2008)
  • Author(s): Matsui H
  • Journal Title: Ann Rheum Dis. 67 Pages: 571-572
  • Peer Reviewed
• [Journal Article] Cyclosporine treatment in the refractory thrombotic thrombotic thrombodytopenic purpura associated with systemic lupus erythematosus (2007)
  • Author(s): Enami T, Suzuki T, Ito S, YoshimiA, Sugihara M, Mamura M, Hayashi T, Goto D, Matsumoto I, Tsutsumi A, Sumida T.
  • Journal Title: Intern Med. 46 Pages: 1033-1037
  • Peer Reviewed
• [Journal Article] The gene expressions of TNFα TTP, TIA-1 and HuR in the peripheral blood mononuclear cells of patients with rheumatoid arthritis before and after infliximab therapy (2007)
  • Author(s): Sugihara M, Tsutsumi A, Suzuki E, Suzuki T, Ogishima H, Hayashi T, Chino Y, Ishii W, Mamura M, Goto D, Matsumoto I, Ito S, Sumida T.
  • Journal Title: Arthritis Rheum. 56 Pages: 2160-2169
  • Peer Reviewed
• [Journal Article] DNA microarray analysis of labial salivary gland of patients with Sjogren's syndrome (2007)
  • Author(s): Wakamatsu E, Nakamura Y, Matsumoto I, Goto D, Ito S, Tsutsumi A, Sumida T.
  • Journal Title: Ann Rheum Dis. 66 Pages: 844-845
  • Peer Reviewed
• [Journal Article] Sarcoid myositis with muscle weakness as a presenting symptom (2007)
  • Author(s): Yamada H, Ishii W, Ito S, Iwanami K, Ogishima H, Suzuki T, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T.
  • Journal Title: Mod Rheumatol 17 Pages: 243-246
  • Peer Reviewed
• [Journal Article] Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease (2007)
  • Author(s): Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T.
  • Journal Title: Intern Med. 46 Pages: 771-774
  • NAID: 130000076731
  • Peer Reviewed
• [Journal Article] A multi-center phase I/II trial of rituximab for refractory systemic lupus erythematosus (2007)
  • Author(s): Tanaka Y, Yamamoto K, Takeuchi T, Nishimoto N, Miyasaka N, Sumida T, Shima Y, Takada K, Matsumoto I, Saito K, Koike T.
  • Journal Title: Mod Rheumatol 17 Pages: 191-197
  • Peer Reviewed
• [Journal Article] Biased usage of synovial immunoglobulin heavy chain variable region 4 by the anti-glucose-6-phosphate isomerase antibody in patients with rheumatoid arthritis (2007)
  • Author(s): Hayashi T, Matsumoto I, Yasukochi T, Mamura M, Goto D, Ito S, Tsutsumi A, Sumida T.
  • Journal Title: Int J Mol Med. 20 Pages: 247-253
  • Peer Reviewed
• [Journal Article] The gene expressions of TNFα TTP, TIA-1 and HuR in the peripheral blood mononuclear cells of patients with rheumatoid arthritis before and after infliximab therapy. (2007)
  • Author(s): Sugihara M
  • Journal Title: Arthritis Rheum. 56 Pages: 2160-2169
  • Peer Reviewed
• [Presentation] 自己免疫性関節炎におけるIL-6とTh17-関節リウマチでの制御の現状- (2008)
  • Author(s): 松本功
  • Organizer: 第38回日本免疫学会総会クリニカルセミナー3
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] 自己免疫関節炎における炎症性サイトカイン制御メカニズム-TH17細胞の関与を含めて- (2008)
  • Author(s): 松本功
  • Organizer: 第52回日本リウマチ学会総会・学術集会イブニングセミナー3
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] 自己免疫関節炎における炎症性サイトカイン制御メカニズム-TH17細胞の関与を含めて- (2008)
  • Author(s): 松本功
  • Organizer: 第52回日本リウマチ学会総会・学術集会イブニングセミナー
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] Therapeutic Effects of Tnf α Antagonist, IL-6 Antagonist and Ctla-4 Ig in Glucose-6-phosphate Isomerase Induced Arthritis. (2007)
  • Author(s): Matsumoto I
  • Organizer: 2007ANNUAL SCIENTIFIC MEETING on the ACR
  • Place of Presentation: ボストン(アメリカ)
  • Year and Date: 2007-11-09
• [Presentation] CTLA-4 Ig, TNFαアンタゴニストはGPI誘導関節炎を抑制する (2007)
  • Author(s): 松本 功
  • Organizer: 第51回日本リウマチ学会総会・学術集会
  • Place of Presentation: 横浜
• [Book] リウマチ科 (2009)
  • Author(s): 松本功、岩波慶一
  • Publisher: 自己免疫性関節炎におけるIL-6/IL-17の役割
• [Book] 自己免疫性関節炎におけるIL-6/IL-17の役割 (2008)
  • Author(s): 松本功
  • Total Pages: 8
  • Publisher: 科学評論社 リウマチ科 41巻
• [Book] Annual review免疫 (2007)
  • Author(s): 松本 功
  • Total Pages: 6
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/clinical-med/rheumatology
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/clinical-med/rheumatology/
• [Patent(Industrial Property Rights)] 関節炎誘発ペプチド (2008)
  • Inventor(s): 松本功、住田孝之、岩波慶一
  • Industrial Property Rights Holder: 国立大学法人筑波大学
  • Industrial Property Number: 2008-022714
  • Filing Date: 2008-02-01
• [Patent(Industrial Property Rights)] 関節炎誘発ペプチド (2008)
  • Inventor(s): 松本功 住田孝之 岩波慶一
  • Industrial Property Rights Holder: 松本功 住田孝之 岩波慶一
  • Filing Date: 2008-11-26
  • Overseas
• [Patent(Industrial Property Rights)] 関節炎誘発原生ペプチド (2008)
  • Inventor(s): 松本 功, 住田孝之, 岩波慶一
  • Industrial Property Rights Holder: 松本 功, 住田孝之, 岩波慶一
  • Industrial Property Number: 2008-022714
  • Filing Date: 2008-02-01