Systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and Sjögren’s syndrome are four major autoimmune rheumatic diseases characterized by the presence of autoantibodies, caused by a dysregulation of the immune system that leads to a wide variety of clinical manifestations. These conditions present complex etiologies strongly influenced by multiple environmental and genetic factors. The human leukocyte antigen (HLA) region was the first locus identified to be associated and still represents the strongest susceptibility factor for each of these conditions, particularly the HLA class II genes, including DQA1, DQB1, and DRB1, but class I genes have also been associated. Over the last two decades, the genetic component of these disorders has been extensively investigated and hundreds of non-HLA risk genetic variants have been uncovered. Furthermore, it is widely accepted that autoimmune rheumatic diseases share molecular disease pathways, such as the interferon (IFN) type I pathways, which are reflected in a common genetic background. Some examples of well-known pleiotropic loci for autoimmune rheumatic diseases are the HLA region, DNASEL13, TNIP1, and IRF5, among others. The identification of the causal molecular mechanisms behind the genetic associations is still a challenge. However, recent advances have been achieved through mouse models and functional studies of the loci. Here, we provide an updated overview of the genetic architecture underlying these four autoimmune rheumatic diseases, with a special focus on the HLA region.

系统性红斑狼疮、系统性硬化症、类风湿性关节炎和干燥综合征是四种主要的自身免疫性风湿病，其特征是存在自身抗体，由免疫系统失调引起，导致多种临床表现。这些情况呈现复杂的病因，受多种环境和遗传因素的强烈影响。人类白细胞抗原 (HLA) 区域是第一个被鉴定为相关的基因座，并且仍然代表这些条件中每一个的最强易感因素，特别是 HLA II 类基因，包括DQA1、DQB1和DRB1, 但 I 类基因也与之相关。在过去的二十年中，这些疾病的遗传成分已得到广泛研究，并发现了数百种非 HLA 风险遗传变异。此外，人们普遍认为，自身免疫性风湿病共享分子疾病途径，例如 I 型干扰素 (IFN) 途径，这反映在共同的遗传背景中。一些众所周知的自身免疫性风湿病多效基因座的例子是 HLA 区域、DNASEL13、TNIP1和IRF5，等等。确定遗传关联背后的因果分子机制仍然是一个挑战。然而，最近的进展是通过小鼠模型和基因座的功能研究取得的。在这里，我们对这四种自身免疫性风湿病的遗传结构进行了更新概述，特别关注 HLA 区域。