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

本研究拟从MHCⅱ类和MHCⅲ类研究类风湿关节炎（RA）的遗传背景，并探讨RA的发病机制。结果表明，位于HLA drβ链第70 ~ 74位的QRRAA氨基酸编码序列与RA的相关性最强。该序列在Dw15、DR1、Dw16中普遍存在，与Dw4、DR10在该位置的氨基酸序列非常相似。表明该序列有可能是易感序列。该序列也与韩国RA有关，并且在韩国也观察到一个序列QKRAA对RA的贡献。此外，HLA链的整个构象也被认为是重要的。另一方面，C4AQ0与日本RA相关，尽管C4AQ0没有高加索型缺失。C4AQ0与QRRAA和任何特定DR类型无关。在韩国，C4AQ0略有增加，但不显著。C4B5…More的频率增加，并且在日本和韩国都观察到C4B5与Dw15的关联。无高加索型缺失的C4AQ0在SLE和PSS中均升高。本研究系列中未缺失C4AQ0纯合子患者。遗传因素对疾病进展、类风湿因子阳性和炎症等临床特征无影响。这些数据表明，即使患者的遗传背景不同，他们的临床过程也几乎相似。但通过Hayashi II的统计方法，可以根据遗传参数对患者进行分类。为了探讨QRRAA在RA发病机制中的作用，我们进行了同源性搜索。有几种药剂被发现具有类似的序列。其中，RA患者抗eb病毒抗体高滴度，但与QRRAA阳性及临床特征无关。腺病毒V型抗体在RA和正常对照组之间也无差异。在RA中检测到针对含QRRAA合成肽的自身抗体，且在有QRRAA的RA患者中阳性率较高。RA患者滑液中也有自身抗体，但其致病意义尚不清楚。我们的研究数据表明，遗传因素在RA的发病过程中起着重要作用。今后继续研究遗传因素与RA发病机制的关系以及病毒等环境因素对RA发病机制的影响具有重要意义。少

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