| Project/Area Number |
07457128
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | ST.MARIANNA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
SAKANE Tsuyoshi St.Marianna University School of Medicine, Departments of Immunology and Medicine.Chief Professor, 医学部, 教授 (40127519)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Noboru St.Marianna University School of Medicine, Institute of Medical Sclence. Senlor, 助教授 (40235982)
中島 敏治 聖マリアンナ医科大学, 難病治療研究センター, 助手 (70247401)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | systemic lupus erythematosus / lupus nephritis / A30 gene / positive charge / receptor editing / genetics / polymorphism / 陽性荷電 / 多型性 / 抗DNA抗体 / 胚細胞型免疫グロブリン遺伝子 / receptor editing / 自己抗体 |
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| Research Abstract |
We found previously that cationic anti-DNA autoantibodies have nephritogenic potential and usage of a specific germline Vk gene, A30, has major influences on cationic charge of the autoantibodies in human lupus nephritis. By using PCR technique, we found that A30 gene locus in the genome was defective in 8 out of 9 SLE patients without nephritis. In contrast, 9 out of 9 patients with lupus nephritis had intact A30 gene. The presence or absence of A30 gene was associated with the development of lupus nephritis or not. It is reported the A30 is a potentially functional but rarely expressed Vk gene in humans. It is possible that normal B cells edit primarily rearranged A30 gene with autoreactive potentials by receptor editing mechanism, for changing the affinity of the B cell Ag receptor to avoid self-reactivity, whereas SLE B cells mayhave a defect in this mechanism. Indeed, we found that normal B cells edit A30-JK2 gene in their genome possibly by inversion mechanism, whereas SLE B cells contain rearranged A30-Jk2-Ck gene in the genome and express A30-associated mRNA,suggesting that receptor editing mechanism is also defective in patients with SLE.Our study suggests that polymorphism of lg Vk locus, and failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.
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