Total analysis of RP105 molecule on B cells : Its function and application to treatment in autoimmune diseases
| Project/Area Number |
18591115
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Saga University |
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Principal Investigator |
NAGASAWA Kohei Saga University, Faculty of Medicine, Professor (00108721)
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| Co-Investigator(Kenkyū-buntansha) |
KOARADA Syuichi Saga University, Faculty of Medicine, Assistant Professor (50304887)
TADA Yoshifumi Saga University, Faculty of Medicine, Associate Professor (70284627)
KIMOTO Masao Saga University, Faculty of Medicine, Professor (40153225)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,760,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | RP105 / B cells / Siogren's svdrome / Autoimmune diseases / Infectious diseases / TLR4 / Collgeen induced arthritis / BCMA / SLE / CD40L / DNAチップ / 自己抗体 / BAFF |
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| Research Abstract |
Through series of studies, we have already demonstrated that B cells lacking RP105 can produce autoantibodies playing an important role in the pathogenesis of systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and dermatomyositis (DM). On the accumulation of these results, we obtained the results during this period shown as below.
1) The infiltration of RP105(-) B cells were dominant in the salivary gland in SS patients and was correlated with the serum level of immunoglobulins(Ig), suggesting that those B cells may be associated with the production of Ig and tissue damage of salivary gland.
2) The expression of Toll like receptor 4 (TLR4), intimately associated with RP105, on monocytes from patients with acute infectious diseases was enhanced and it was suggested that induction of TLR4 expression may play a role in the protection against infection.
3) We made genetically RP105-deleted mice and investigated the development of collagen-induced arthritis (CIA), a model of rheumatoid arthritis. It was found that the incidence and severity of CIA was increased in RP105-deleted mice, suggesting that RP105 might have a regulatory function against excessive immune response.
4) For the approach to a new treatment of autoimmune diseases, we are searching for molecules specifically expressed on RP105 (-)B cells using DNA microarray method. We found that BCMA was specifically expressed on RP105 (-) B cells and implication of BCMA on human B cells was first established. We are now trying to produce monoclonal antibodies against BCMA. This will be a new approach to treatment of autoimmune diseases.
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Report
(3 results)
Research Products
(43 results)
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[Journal Article] Increase of RP105-lacking activated B cell in the peripheral blood and salivary glands in patients with Sjogren's syndrome2008
Author(s)
Kikuchi Y, Koarada S, Nakamura S, Yonemitsu N, Tada Y, Haruta Y, Morito F, Ohta A, Miyake K, Horiuchi T, Nagasawa K.
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Journal Title
Clin Exp Rheumatol 26
Pages: 5-12
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] High-resolution computed tomography characterization of interstitial lung diseases in polymyositis/dermatomyositis2008
Author(s)
Hayashi S, Tanaka M, Kobayashi H, Nakazono T, Satoh T, Fukuno Y, Arakane N, Tada Y, Koarada S, Ohta A, Nagasawa K.
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Journal Title
J Rheumatol 36
Pages: 260-269
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Increase of RP105-lacking activated B cells in the peripheral blood and salivary glands in patients with Sjogren's syndrome2008
Author(s)
Kikuchi Y, Koarada S, Nakamura S, Yonemitsu N, Tada Y, Haruta Y, Morito F, Ohta A, Miyake K, Horiuchi T, Nagasawa K
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus:a case-control study and a meta-analysis2007
Author(s)
Horiuchi T, Kiyohara C, Tsukamoto H, Sawabe T, Furugo I, Yoshizawa S, Ueda A, Tada Y, Kimoto Y, Mitoma H, Harashima S, Yoshizawa S, Shimoda T, Okamura S, Nagasawa K, Harada M.
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Journal Title
Ann Rheum Dis 66
Pages: 320-324
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case-control study and a meta-analysis2007
Author(s)
Horiuchi T, Kiyohara C, Tsukamoto H, Sawabe T, Furugo I, Yoshizawa S, Ueda A, Tada Y, Kimoto Y, Mitoma H, Harashima S, Yoshizawa S, Shimoda T, Okamura S, Nagasawa K, Harada M.
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Journal Title
Ann Rheum Dis 66
Pages: 320-324
Related Report
Peer Reviewed
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