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自身免疫性疾病中可能存在的发育调控重链可变区基因缺失。

Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases.

作者信息

Yang P M, Olsen N J, Siminovitch K A, Olee T, Kozin F, Carson D A, Chen P P

机构信息

Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037.

出版信息

Proc Natl Acad Sci U S A. 1990 Oct;87(20):7907-11. doi: 10.1073/pnas.87.20.7907.

DOI:10.1073/pnas.87.20.7907
PMID:2122448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC54860/
Abstract

Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. We have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/P1) related to both anti-DNA and anti-IgG autoantibodies, we studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (VH) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important VH genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.

摘要

几个与自身抗体相关的可变区（V）基因在个体发育早期优先表达，这强烈表明它们具有发育和生理重要性。因此，这些基因中一个或多个的多态性可能会改变自身免疫性疾病的易感性。我们广泛搜索了与发育调控的V基因相关的探针，该探针能够区分人群中高度同源的V基因。使用与抗DNA和抗IgG自身抗体相关的此类探针（即Humhv3005/P1），我们研究了类风湿性关节炎和系统性红斑狼疮患者的限制性片段长度多态性，发现明显的重链V（VH）基因缺失几乎仅限于自身免疫患者。这些数据表明，生理上重要的VH基因的缺失可能通过对B细胞库的发育和稳态产生间接影响而增加自身免疫的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/b7d9e3c0d821/pnas01045-0121-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/5cb3b0eccb7f/pnas01045-0120-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/ffe90dee0a24/pnas01045-0120-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/b7d9e3c0d821/pnas01045-0121-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/5cb3b0eccb7f/pnas01045-0120-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/ffe90dee0a24/pnas01045-0120-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ab/54860/b7d9e3c0d821/pnas01045-0121-a.jpg

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Arthritis Rheum. 1982 Nov;25(11):1271-7. doi: 10.1002/art.1780251101.
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片段重复是导致人类免疫球蛋白重链可变区多样性的驱动力之一。
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