RFLP analysis of HLA and T cell receptor genes in sarcoidosis

结节病是一种病因不明的全身性肉芽肿性疾病。结节病的发病机制尚不清楚，但一些检查提示患者存在免疫功能紊乱或遗传机制。我们以前报道了一个显着的关联与HLA-DRw 52 atitigeri结节病。本研究对结节病患者的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。以HLA DR β、DQ α、DQ β和T细胞受体α链和β链的cDNA为探针，通过RFLP分析，可以检测出常规血清学分型方法无法区分的HLA DR β基因多态性。DRbeda基因的5个限制性片段仅见于DRw 52阳性个体，且在患者中的频率高于对照组，但没有特异性片段。确切个体的碎片模式彼此相似，根据碎片的存在将患者分为两组。DQ α和DQ β基因的RFLP分析也比血清学方法发现更多的多态性，但DQ基因之间没有明显的关联。这些结果表明DR抗原在结节病的发病中起主要作用，而T细胞受体基因在结节病患者中未发现特异性的V区重排。T细胞受体基因限制性片段频率在患者组和对照组之间无显著性差异。这些结果表明，可能存在引起结节病的异质性抗原。

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.