| Project/Area Number |
01480214
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Tohoku University |
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Principal Investigator |
SASAKI Takeshi 2nd Department of Internal Medicine, Tohoku University School of Medicine, Associate Professor, 医学部, 助教授 (50110656)
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| Co-Investigator(Kenkyū-buntansha) |
SANO Hiroshi Biotechnology Instutute, Akita Prefectural College of Agriculture, Professor, 生物工学研究所, 教授 (20178809)
ENDO Kazuyasu 2nd Department of Internal Medicine, Tohoku University School of Medicine, Instr, 医学部付属病院, 講師 (60125507)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | Autoantibody / Anti-DNA Antibody / Immunoglobulin Gene / Systemic Lupus Erythematosus / 抗DMA抗体 / In situ ハイブリダイゼ-ション / 抗DNA抗体 |
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| Research Abstract |
1. We identified specific clonotypes expressing anti-DNA idiotypes (0-81 Id and NE-1 Id) in circulating immune complexes (CIC) of patients with active lupus nephritis. Isoelectrofocusing studies revealed that renal elevates formed three bands with DNA, in which one was identical with that of CIC-derived antibodies. Positive tests for anti-DNA CIC were significantly associated with the incidence of diffuse proliferative glomerulonephritis (DPGN).
2. The analysis of B cell repertoire in patients with SLE revealed that nephritogenic 0-81 Id- or NE-1-Id-positive clones at precursor level tended to increase in lupus patients. DNA sequences coding the variable regions of anti-DNA clones, NE-l and NE-13 were identical with the germline gene, VH4.21, and Vk gene segments with Vk21b. These data indicates that antigen-driven somatic mutations may have no important role to play in the expansion of some IgM clones associated with pathogenetic anti-DNA Ab in SLE.
3. We studied VH gene family usages on B cells from patients with SLE. Dot blot hybridization and northern blot analysis revealed that the SLE B cells may preferentially use VH I and VH IV, which often encode autoantibodies with polyspecificity. We also developed in situ hybridization technique for the detection of VH gene at clonal level.
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