Department of Systemic Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland.
Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland.
Cells. 2020 May 2;9(5):1127. doi: 10.3390/cells9051127.
Rheumatoid arthritis (RA) is an autoimmune disease with an unclear pathogenic mechanism. However, it has been proven that the key underlying risk factor is a genetic predisposition. Association studies of the HLA-DRB1 gene clearly indicate its importance in RA morbidity. This review presents the current state of knowledge on the impact of HLA-DRB1 gene, functioning both as a component of the patient's genome and as an environmental risk factor. The impact of known HLA-DRB1 risk variants on the specific structure of the polymorphic HLA-DR molecule, and epitope binding affinity, is presented. The issues of the potential influence of HLA-DRB1 on the occurrence of non-articular disease manifestations and response to treatment are also discussed. A deeper understanding of the role of the HLA-DRB1 gene is essential to explore the complex nature of RA, which is a result of multiple contributing factors, including genetic, epigenetic and environmental factors. It also creates new opportunities to develop modern and personalized forms of therapy.
类风湿关节炎（RA）是一种病因不明的自身免疫性疾病。然而，已经证明其关键的潜在风险因素是遗传易感性。HLA-DRB1 基因的关联研究清楚地表明了它在 RA 发病机制中的重要性。这篇综述介绍了 HLA-DRB1 基因的最新研究进展，该基因不仅是患者基因组的组成部分，也是环境风险因素。本文介绍了已知的 HLA-DRB1 风险变体对多态性 HLA-DR 分子特定结构和表位结合亲和力的影响。还讨论了 HLA-DRB1 对关节外疾病表现和治疗反应的潜在影响。深入了解 HLA-DRB1 基因的作用对于探索 RA 的复杂性质至关重要，RA 是由多种因素共同作用的结果，包括遗传、表观遗传和环境因素。它还为开发现代和个性化的治疗方法创造了新的机会。
