Department of Rheumatology, Leiden University Medical Center RC, The Netherlands.
Immunogenetics. 2011 Aug;63(8):459-66. doi: 10.1007/s00251-011-0528-6. Epub 2011 May 10.
Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 0.5-1% of the population worldwide. The disease has a heterogeneous character, including clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although the pathogenesis of RA is poorly understood, progress has been made in identifying genetic factors that contribute to the disease. The most important genetic risk factor for RA is found in the human leukocyte antigen (HLA) locus. In particular, the HLA molecules carrying the amino acid sequence QKRAA, QRRAA, or RRRAA at positions 70-74 of the DRβ1 chain are associated with the disease. The HLA molecules carrying these "shared epitope" sequences only predispose for ACPA-positive disease. More than two decades after the discovery of HLA-DRB1 as a genetic risk factor, the second genetic risk factor for RA was identified in 2003. The introduction of new techniques, such as methods to perform genome-wide association has led to the identification of more than 20 additional genetic risk factors within the last 4 years, with most of these factors being located near genes implicated in immunological pathways. These findings underscore the role of the immune system in RA pathogenesis and may provide valuable insight into the specific pathways that cause RA.
类风湿关节炎（RA）是一种影响全球 0.5-1%人口的慢性自身免疫性疾病。该疾病具有异质性特征，包括抗瓜氨酸蛋白抗体（ACPA）阳性和 ACPA 阴性疾病的临床亚群。尽管 RA 的发病机制尚未完全阐明，但在确定导致该疾病的遗传因素方面已经取得了进展。RA 最重要的遗传风险因素位于人类白细胞抗原（HLA）基因座。特别是在 DRβ1 链的 70-74 位氨基酸序列中携带 QKRAA、QRRAA 或 RRRAA 的 HLA 分子与该疾病相关。携带这些“共享表位”序列的 HLA 分子仅使 ACPA 阳性疾病易感性增加。在发现 HLA-DRB1 作为遗传风险因素二十多年后，于 2003 年确定了 RA 的第二个遗传风险因素。新技术的引入，如全基因组关联分析方法，导致在过去 4 年内鉴定出了 20 多个额外的遗传风险因素，其中大多数因素位于免疫途径相关基因附近。这些发现强调了免疫系统在 RA 发病机制中的作用，并可能为导致 RA 的特定途径提供有价值的见解。
