A study of HLA-region genes and their products in patients with autoimmune diseases.

人类组织相容性复合体(HLAs)中至少有一个或几个基因在自身免疫性疾病的发病过程中发挥作用。在高加索人群中，人类白细胞抗原DR3、DQ2基因携带者对系统性红斑狼疮(SLE)、干燥综合征(SS)、重症肌无力(MG)、系统性硬化症(SSc)等自身免疫性疾病的易感性较高。然而，在日本，上述疾病的易感基因(S)仍不清楚。我采用血清学方法、基因组DNA限制性片段长度多态性(RFLP)、第II类基因等位基因，以及补体4(C4)等位基因在86例SLE、69例SS、74例MG、SSC患者中进行了研究SSc 33例，多发性肌炎和/或混合性结缔组织病(PM/MCTD)36例。研究结果如下：1)在系统性红斑狼疮患者中，人类白细胞抗原-DR4阳性者更易患狼疮性肾炎，但对中枢神经…受累有抵抗力。S系统比没有DR4的系统多。SLE患者C4a基因零等位基因(C4AQ0)频率高于对照组，但RFLP方法未检测到C4a基因缺失。2)女性MG患者的HLADR53、DPB1*0201和DQA1*03频率均高于对照组。结果表明，日本重症肌无力患者至少可以分为两个不同的组。第一组包括起病早、DR53、DPB1*0201和DQ1*03频率较高的女性。第二组由发病较晚的男性和女性组成，未发现与第二组相关的特定的人类白细胞抗原等位基因。此外，至少有两个不同的HLAII类基因在年轻女性MG型疾病的发病中起作用。3)在SSc中，有肺纤维化的患者的HLADR2、C4BQ0和抗SCL70抗体的频率高于无肺纤维化的患者。因此，在疾病的早期阶段仔细监测和治疗可能对患者有必要使用DR2和C4BQ0。较少

At least one or several genes in human histocompatibility complex (HLA) play roles on the disease process of autoimmune diseases. In Caucasian, it is well established that individuals carrying HLA-DR3,DQ2 are more susceptible to many autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), myasthenia gravis (MG), systemic sclerosis (SSc).In Japanese, however, susceptible gene(s) in the HLA region of diseases listed above are still unclear.I studied HLA specificities by serological method, restriction fragment length polymorphism (RFLP) of genomic DNA, alleles of class II genes by using polymerase chain reaction-RFLP, and complement 4 (C4) allotypes in 86 patients of SLE, 69 of SS, 74 of MG, 33 of SSc and 36 of polymyositis and/or mixed connective tissue disease (PM/MCTD). The results obtained were as follows.1) Among SLE patients, individuals positive for HLA-DR4 are more susceptible to lupus nephritis, but resistant to the involvement of central nervou … More s system than those without DR4. The frequency of the null allele of C4A gene (C4AQ0) is higher in SLE patients than in controls, however, deletion of C4A gene was not detected by RFLP method.2) Higher incidences of HLA-DR53, DPB1*0201 and DQA1*03 were observed in female patients with MG when compared with the controls. The results indicate that Japanese patients with MG can be subdivided into at least two distinct groups. The first group consists of females whose disease onset is early and who have a high frequency of DR53, DPB1*0201 and DQ1*03. The second group consists of males and females with late onset of disease.No particular HLA allele was found to be associated with the second group. Furthermore at least two distinct HLA class II genes were suggested to play roles on the disease onset of young females with MG.3) Among SSc, the frequencies of HLA-DR2, C4BQ0 and anti-Scl 70 antibody were higher in patients with pulmonary fibrosis than those without it. Therefore, careful monitoring and treatment at an early stage of disease may necessary in patients the DR2 and C4BQ0. Less