Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, New York, USA
Ann Rheum Dis. 2023 Aug;82(8):999-1014. doi: 10.1136/ard-2022-223741. Epub 2023 Feb 15.
Research elucidating the pathogenesis of systemic lupus erythematosus (SLE) has defined two critical families of mediators, type I interferon (IFN-I) and autoantibodies targeting nucleic acids and nucleic acid-binding proteins, as fundamental contributors to the disease. On the fertile background of significant genetic risk, a triggering stimulus, perhaps microbial, induces IFN-I, autoantibody production or most likely both. When innate and adaptive immune system cells are engaged and collaborate in the autoimmune response, clinical SLE can develop. This review describes recent data from genetic analyses of patients with SLE, along with current studies of innate and adaptive immune function that contribute to sustained IFN-I pathway activation, immune activation and autoantibody production, generation of inflammatory mediators and tissue damage. The goal of these studies is to understand disease mechanisms, identify therapeutic targets and stimulate development of therapeutics that can achieve improved outcomes for patients.
阐明系统性红斑狼疮（SLE）发病机制的研究已经确定了两类关键的介质，即 I 型干扰素（IFN-I）和针对核酸及核酸结合蛋白的自身抗体，它们是疾病的重要贡献者。在重大遗传风险的肥沃背景下，一个触发因素，可能是微生物，会诱导 IFN-I、自身抗体产生或很可能两者同时产生。当先天和适应性免疫系统细胞参与并协同自身免疫反应时，就会出现临床 SLE。这篇综述描述了来自 SLE 患者的遗传分析的最新数据，以及目前关于先天和适应性免疫功能的研究，这些研究有助于持续的 IFN-I 途径激活、免疫激活和自身抗体产生、炎症介质的产生和组织损伤。这些研究的目的是了解疾病机制，确定治疗靶点，并刺激开发能够改善患者预后的治疗方法。
