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Study for genetical background of arthritis rheumatism on MNC clacc II and III antigens.

MNC clacc II 和 III 抗原的风湿关节炎遗传背景研究。

基本信息

批准号：
02670268
负责人：
TAKEUCHI Fujio
金额：
$ 1.66万
依托单位：
Tokyo 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：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

In this research program, genetical background of rheumatoid arthritis (RA) were studied on MHC class II and III, and pathogenesis of RA was discussed. It was confirmed that the sequence coding the amino acids QRRAA located at the position of 70 - 74 on HLA DRbeta chain, was most strongly associated with RA. The sequence is common among Dw15, DR1, Dw16, and is very closely similar to amino acid sequence of Dw4 and DR10 at the position. It indicated the possibility that the sequence was a susceptible sequence through ethnics. The sequence was also associated with Korean RA and a contribution of a sequence, QKRAA, to RA was also observed in Korea. Still more, whole conformation of HLA chain was also thought to be important. On the other hand C4AQ0 was associated with Japanese RA though the C4AQ0 did not have Caucasian-type deletion. C4AQ0 was not associated with QRRAA and any specific DR types. In Korea the slight increase of C4AQ0 was observed but not significant. The frequency of C4B5 … More was increased and the association of C4B5 with Dw15 was observed in both Japanese and Korean. The C4AQ0 without Caucasian-type deletion was increased in both SLE and PSS. No patient with homozygote of C4AQ0 was deleted in this research series. The genetic factors did not affect on clinical features such as progression of the disease, positivity of rheumatoid factor and inflammation. These data suggested that patients would take almost similar clinical course even if their genetical backgrounds were different. But by the stastical method of Hayashi II, patients could be clasterized according to genetical parameters. For investigating the contribution of QRRAA to the pathogenesis of RA, homology search was carried out. Several agents were revealed to have the similar sequence. Among them, high titer of anti-EB virus antibody was observed in RA but it was not associated with the positivity of QRRAA and with clinical features. Antibody to adenovirus type V was not different between RA and normal control either. Auto-antibody against the synthetic peptide containing QRRAA was detected in RA and the positivity was high in RA patients with QRRAA. The auto-antibody was also observed in synovial fluid of RA patients but the pathogenic significance was unclear. Our data in the study make it clear that genetic factors play an important role in pathgenesis of RA. It would be important to study continuously the association of genetic factors with etiological mechanism of RA and environmental factors such as virus et al. in the future. Less

本研究从MHC Ⅱ类和Ⅲ类分子水平探讨类风湿关节炎（RA）的遗传背景，探讨RA的发病机制。结果表明，HLA DR β链70 ~ 74位氨基酸的编码序列QRRAA与RA的相关性最强。该序列在Dw 15、DR 1、Dw 16中是共同的，并且在该位置与Dw 4和DR 10的氨基酸序列非常相似。提示该序列可能是一个种族易感序列。该序列也与韩国RA和一个序列，QKRAA，RA的贡献，也观察到在韩国。此外，HLA链的整体构象也被认为是重要的。另一方面，C4 AQ 0与日本RA相关，尽管C4 AQ 0没有高加索型缺失。C4 AQ 0与QRRAA和任何特定DR类型无关。在韩国，观察到C4 AQ 0略有增加，但不显著。C4 B5的频率 ...更多信息 C4 B5与Dw 15的相关性在日本人和韩国人中均观察到。无高加索型缺失的C4 AQ 0在SLE和PSS中均增加。本研究中未发现C4 AQ 0纯合子缺失的病例。遗传因素对疾病进展、类风湿因子阳性、炎症反应等临床特征无影响。这些数据表明，即使患者的遗传背景不同，他们也会采取几乎相似的临床过程。但按Hayashi II的统计方法，可根据遗传参数对患者进行分类。为了研究QRRAA在RA发病机制中的作用，进行了同源性搜索。几种药物被发现具有相似的序列。其中RA患者抗EB病毒抗体滴度较高，但与QRRAA阳性及临床特征无关。抗V型腺病毒抗体在RA组和正常对照组之间也无显著性差异。RA患者血清中可检测到抗QRRAA合成肽的自身抗体，且QRRAA阳性率高。RA患者滑液中也有自身抗体存在，但其致病意义尚不明确。我们的研究数据表明遗传因素在RA的发病机制中起重要作用。今后应继续深入研究遗传因素与类风湿关节炎发病机制及病毒等环境因素的关系。少