Reshaping the shared epitope hypothesis - HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67-74 of the HLA-DRB1 molecule
Reshaping the shared epitope hypothesis - HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67-74 of the HLA-DRB1 molecule
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DOI：
10.1002/art.10210
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发表时间：
2002-04-01
影响因子：
--
通讯作者：
van de Putte, LBA
中科院分区：
文献类型：
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作者：
de Vries, N;Tijssen, H;van de Putte, LBA
目标。进一步分析人类白细胞抗原-DRB1等位基因与新近发病的类风湿关节炎(RA)疾病易感性的关系。对167例高加索类风湿关节炎患者和16 6例健康对照进行了HLADRB1基因分型。在新近发病的RA中，证实了RA的易感性与编码共享表位易感性序列(SESS)的等位基因组有关。在非Sess等位基因中，DRB1*07、*1201、*1301和*1501具有显著的保护作用。即使在校正了Sess等位基因的影响后，仍观察到DRB1等位基因的显著独立保护作用。保护性等位基因共享第三个高变区基序。在易感性和保护性等位基因上都观察到了独立的纯合效应。非易感等位基因在RA风险方面存在显著差异。保护性等位基因在67-74位显示出明显的同源性，通常在67位编码异亮氨酸或在70位编码天冬氨酸。易感和保护等位基因均显示纯合子效应。基于这些结果和文献报道的数据，为了纳入非易感等位基因之间风险差异的发现，我们建议重塑共同表位假说如下：HIA相关RA的风险是由HLA-DRB1分子67-74位的氨基酸替换编码的。
Objective. To further analyze the association of HLA-DRB1 alleles with disease susceptibility in recent-onset rheumatoid arthritis (RA).Methods. One hundred sixty-seven Caucasian RA patients and 166 healthy controls were typed for HLA-DRB1.Results. The association of susceptibility to RA with the group of alleles encoding the shared epitope susceptibility sequences (SESSs) was confirmed in recent-onset RA. Among non-SESS alleles, DRB1*07, *1201, *1301, and *1501 showed significant protective effects. Even after correction for the influence of SESS alleles, significant independent protective effects of DRB1 alleles were observed. Protective alleles shared a third hypervariable region motif. Independent homozygosity effects were observed both for susceptibility and for protective alleles.Conclusion. Nonsusceptibility alleles differ significantly with regard to RA risk. Protective alleles show clear homology at positions 67-74, often encoding isoleucine at position 67 or aspartic acid at position 70. Susceptibility and protective alleles both show homozygosity effects. Based on these results and on data reported in the literature, in order to incorporate the finding of differential risks among nonsuseeptibility alleles, we propose to reshape the shared epitope hypothesis as follows: HIA-associated risk for RA is encoded by amino acid substitutions at positions 67-74 of the HLA-DRB1 molecule.