| Project/Area Number |
09670561
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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 |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SAKAMAKI Sumio Sapporo Medical University, School of Internal Medicine, Medicine, 4th Department of Assistant Professor, 医学部, 講師 (00196081)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYAMA Tetsuji Sapporo Medical University, School of Medicine, 4th Department of Internal Medic, 医学部, 助手 (10284994)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | HLA-DPAw9 / ADCC / Tropomyosin / ELISA / Peptide / Transgenic mice |
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| Research Abstract |
Background & Aims : Recent studies suggest that tropomyosin (TM) may act as a putative autoantigen in ulcerative colitis (UC). Recently, we identified by computer homology analysis a specific peptide (HIAEDADRK) in human TM that can bind to HLA-DPw9. This specific HLA molecule was also reported to be associated with UC patients in Japan. The aim of this study was to investigate the role of HLA-DPw9 in pathogenesis of UC by checking antibody against this specific peptide associated with HLA-DPw9 and establishing a UC model using HLA-DPw9 transgenic mice. Methods : (1) Antibodies were measured by ELISA with a synthetic peptide in 20 healthy volunteers, 48 patients with UC, 26 with Crohn's disease (CD), 3 with primary sclerosing cholangitis (PSC), and 6 with primary biliary cirrhosis (PBC). The functional significance of antibodies was investigated by antibody dependent cell mediated cytotoxicity (ADCC) against DPw9 transfected L cells by standard 51Cr release assay. (2) To investigate wh
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ether HLA-DPw9 transgenic mice develop UC, they were treated with TAK 603 (T helper 1 specific inhibitor provided by TAKEDA Co. Ltd.).
Results : (1) OD values of sera from UC (1.50*0.47) and PSC (1.90*0.11) were significantly higher than those from healthy volunteers (0.62*0.24) (p<O.05), CD (0.73*0.35) (p<O.05) and PBC (0.45*0.12) (p<O.O5). The values in UC decreased with clinical improvement. The ADCC activity of UC sera correlated well to the antibody titer against this synthetic peptide.
(2) HLA-DPw9 transgenic mice did not develop UC by TAK 603.
Conclusions : In this study, we revealed that a specific epitope of TM was capable of humoral immune response in patients with UC and PSC.This may provide important biochemical information to explain the autoimmune mechanism in UC and PSC, and may help in the development of strategies for possible immune therapy such as antigen-based immunointervention utilizing this specific pepticte, For developing UC in HLA-DPw9 transgenic mice other agent triggering inflammation than TAK 603 will benecessary. Less
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