1999 Fiscal Year Final Research Report Summary
Analysis of T cell epitopes in the patients with the antiphospholipid syndrome.
| Project/Area Number |
09670461
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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 |
内科学一般
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
TSUTSUMI Akito Hokkaido Univ., Sch. Med., Assi. Pro., 医学部, 助手 (60250453)
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| Project Period (FY) |
1997 – 1999
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| Keywords | antiphospholipid syndrome / anti-α2glycoprotein I antibody / anticardiolipin antibody / α2glycoprotein I / epitope / polymorphism |
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| Research Abstract |
I) Efforts were made to establish monoclonal anti-βィイD22ィエD2-GPI and anti-prothrombin antibodies from peripheral blood lymphocytes of patients with antiphospholipid syndrome (APS).
ii) A random peptide library was screened to identify the B cell epitope of anti-βィイD22ィエD2-GPI antibodies established from APS patients. Putative epitopes were identified on domain IV of the βィイD22ィエD2-GPI protein.
iii) Among the known polymorphisms of βィイD22ィエD2-GPI, ィイD1247ィエD1Val/Leu polymorphism was associated with prevalence of anti-βィイD22ィエD2-GPI antibodies. A monoclonal anti-βィイD22ィエD2-GPI antibody was found to bind to ィイD1247ィエD1ValβィイD22ィエD2-GPI more strongly than to ィイD1247ィエD1LeuβィイD22ィエD2-GPI.
iv) Peripheral blood T lymphocytes from APS were tested for their response against ィイD1247ィエD1ValβィイD22ィエD2-GPI and ィイD1247ィエD1LeuβィイD22ィエD2-GPI. A large heterogeneity was observed among individual patients, suggesting the importance of this polymorphism in βィイD22ィエD2-GPI induced T cell response.
v) Two families with βィイD22ィエD2-GPI deficiency were identified. βィイD22ィエD2-GPI deficient individuals had a homozygous deletion in the 4ィイD1thィエD1 exon of βィイD22ィエD2-GPI. βィイD22ィエD2-GPI deficient individuals did not show significant abnormalities in hemostasis or lipid metabolism. Persons with hetorozygous deficiency were found in 6.3% of the studied population.
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[Publications] Yasuda S, Tsutsumi A, Chiba H, Yanai H, Miyoshi Y, Takeuchi R, Horita T, Kasahara K, Atsumi T, Ichikawa K, Matsuura E, Koike T.: "β2-glycoprotein I deficiency : prevalence, genetic background and effect on plasma lipoprotein metabolism."Atherosclerosis. (in press).
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「研究成果報告書概要(欧文)」より
