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

自身免疫性疾病患者 HLA 区基因及其产物的研究。

基本信息

批准号：
03670338
负责人：
MORIUCHI Junko
金额：
$ 1.34万
依托单位：
Tokai University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670338/
关键词：
Systemic lupus erythematosus Sjogren's syndrome Myasthenia gravis Systemic sclerosis Mixed connective tissue disease HLA RFLP Complemeny C4 シェークシン症候群全身性エリテマト-デス RFLp 自己免疫疾患自己抗体

项目摘要

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

人组织相容性复合体（HLA）中至少有一个或几个基因参与自身免疫性疾病的发病过程。在白种人中，携带HLA-DR3、DQ2的个体更容易患许多自身免疫性疾病，如系统性红斑狼疮（SLE）、干燥综合征（SS）、重症肌无力（MG）、系统性硬化症（SSc）。然而，在日本，上述疾病HLA区域的易感基因仍不清楚。我对86例SLE患者、69例SS患者、74例MG患者、33例SSc患者和36例多发性肌炎和/或混合性结缔组织病（PM/MCTD）患者采用血清学方法研究HLA特异性、基因组DNA限制性片段长度多态性（RFLP）、II类基因等位基因（RFLP）和补体4 （C4）等位型。所得结果如下：1)在SLE患者中，HLA-DR4阳性个体更容易发生狼疮性肾炎，但对中枢神经系统的累及较无DR4者有抵抗力。SLE患者C4A基因空等位基因（C4AQ0）的频率高于对照组，但RFLP法未检测到C4A基因缺失。2)女性MG患者HLA-DR53、DPB1*0201、DQA1*03的发生率高于对照组。结果表明，日本MG患者可以细分为至少两个不同的群体。第一组为发病早、DR53、DPB1*0201、DQ1*03频率较高的女性。第二组包括发病较晚的男性和女性。没有发现特定的HLA等位基因与第二组相关。此外，至少有两种不同的HLA II类基因在年轻女性mg的发病中发挥作用。3)SSc中，肺纤维化患者的HLA- dr2、C4BQ0和抗scl70抗体的频率高于无SSc的患者。因此，对于DR2和C4BQ0患者，在疾病早期进行仔细的监测和治疗可能是必要的。少