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RFLP analysis of HLA and T cell receptor genes in sarcoidosis

结节病 HLA 和 T 细胞受体基因的 RFLP 分析

基本信息

批准号：
01570418
负责人：
ABE Shosaku
金额：
$ 1.22万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

Sarcoidosis is a systemic granulomatous disease with unknown etiology. The pathogenesis of sarcoidosis still remains unclear, but some examinations indicate an immunologic disorder of the patients or the existence of genetic mechanisms. We previously reported a significant association with HLA-DRw52 atitigeri in sarcoidosis. In this study, we performed RFLP analysis of HLA genes arid T cell receptor genes in patients with sarcoidosis. DNA was extracted from peripheral blood lymphocytes of the patients and healthy control subjects. The probes used were cDNA of HL-DRbeta, DQalpha(and DQbeta and T cell receptor alpha and beda chain.The RFLP analysis could detect polymorphism of the HLA-DRbeda gene that was not distinguishable by conventional serological typing. Five restriction fragments of DRbeda gene were only seen in DRw52-positive individuals, and snowed greater frequencies in the patients than in control subjects, although no restriction fragments were specific for sarcoidosis. The patterns of the fragments in exact individual resembled one another, and patients could be divided into two groups according to the presence of the fragments. The RFLP analysis of DQalpha and DQbeta genes also could more minute polymorphism than serological metliods, but a distinct association of DQ genes was not observed. These results indicate that DR antigens play a major role in the pathogenesis of sarcoidosis.As for T cell receptor genes, no specific rearrangement of V region were observed in sarcoidosis patients. Restriction fragments of T cell receptor genes snowed no significant difference in the frequencies between the patients and control subjects. These results suggest that there may be heterogenous antigens that cause sarcoidosis.

结节病是一种病因不明的全身性肉芽肿性疾病。结节病的发病机制仍不清楚，但一些检查表明患者存在免疫紊乱或存在遗传机制。我们之前报道过与结节病中的 HLA-DRw52 atitigeri 显着相关。在这项研究中，我们对结节病患者的 HLA 基因和 T 细胞受体基因进行了 RFLP 分析。从患者和健康对照者的外周血淋巴细胞中提取DNA。所用探针为HL-DRbeta、DQalpha(和DQbeta)以及T细胞受体α和beda链的cDNA。RFLP分析可以检测常规血清学分型无法区分的HLA-DRbeda基因多态性。DRbeda基因的5个限制性片段仅在DRw52阳性个体中出现，并且在患者中出现的频率高于对照尽管没有针对结节病的限制性片段。确切个体的碎片模式彼此相似，根据碎片的存在可以将患者分为两组。 DQα和DQβ基因的RFLP分析也可以比血清学方法更精细的多态性，但没有观察到DQ基因的明显关联。这些结果表明 DR 抗原在结节病患者T细胞受体基因未见V区特异性重排。 T细胞受体基因限制性片段的出现频率在患者和对照受试者之间没有显着差异。这些结果表明可能存在引起结节病的异源抗原。