Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Rheumatology Research Center, Shariati Hospital, Kargar Ave., PO Box 1411713137, Tehran, Iran.
Immunogenetics. 2019 Apr;71(4):283-297. doi: 10.1007/s00251-019-01103-2. Epub 2019 Jan 22.
Systemic lupus erythematosus (SLE) is an autoimmune multi-organ disorder that presents itself in a thousand ways. Its clinical course is extremely unpredictable, which makes diagnosis and treatment a challenge for clinicians. It appears that the clinical course of SLE is determined by genetic material in combination with environmental factors. In this article, we review recent findings on the pathogenesis of SLE from the perspective of genetics, focusing on defects in the clearance of apoptotic bodies and immune complexes, on alterations in the innate immune system response, and on impaired pathways in the adaptive immune system. Furthermore, the major histocompatibility complex (MHC) and non-MHC genes discovered during genome-wide association studies (GWASs) in SLE patients are also evaluated. In addition, the effect of these polymorphisms on the function of their related transcripts and their association with the clinical manifestations of SLE and its pathophysiology are explained. Finally, the association of genetic polymorphisms with clinical responses to common medications used in the treatment of SLE is also discussed.
系统性红斑狼疮（SLE）是一种自身免疫性多器官疾病，其表现形式千差万别。其临床病程极难预测，这使得临床医生的诊断和治疗面临挑战。似乎 SLE 的临床病程是由遗传物质与环境因素共同决定的。在本文中，我们从遗传学的角度综述了 SLE 发病机制的最新研究发现，重点关注凋亡小体和免疫复合物清除的缺陷、固有免疫系统反应的改变以及适应性免疫系统中受损的途径。此外，还评估了 SLE 患者全基因组关联研究（GWAS）中发现的主要组织相容性复合体（MHC）和非 MHC 基因。此外，还解释了这些多态性对其相关转录本功能的影响及其与 SLE 临床表现和病理生理学的关系。最后，还讨论了遗传多态性与治疗 SLE 常用药物临床反应的关系。
