Laurent Arnaud , François Chasset , Thierry Martin
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引用次数: 0
摘要
系统性红斑狼疮(SLE)是一种慢性全身性自身免疫性疾病,其特点是免疫反应失调,导致广泛的炎症和各种器官的损伤。感染、激素影响和紫外线照射等环境因素可诱发具有遗传易感性的个体患病。全基因组关联研究发现了 100 多个与系统性红斑狼疮的免疫调节、干扰素(IFN)信号转导和抗原递呈有关的易感基因位点。此外,罕见的单基因狼疮病例也有助于了解关键的潜在疾病机制。系统性红斑狼疮的自身耐受性丧失和自身免疫反应的持续存在是由多种免疫异常造成的。特别是,由于吞噬和补体激活缺陷导致的凋亡细胞清除缺陷会导致自身抗原的积累。失调的先天性免疫反应激活了适应性免疫系统,扩大了炎症反应,其中I型IFNs发挥了重要作用。B 细胞发育和活化异常会导致产生自体反应性抗体,形成免疫复合物,造成组织损伤。同样,T 细胞分区紊乱、调节性 T 细胞功能改变和细胞因子(尤其是 IFN-α)分泌改变也会造成组织损伤。人们对系统性红斑狼疮免疫发病机制的认识正在迅速发展,目前的研究正在确定新的分子途径和潜在的治疗靶点。未来对系统性红斑狼疮的分类可能会基于潜在的生物学途径,而不仅仅是临床和血清学体征。本综述旨在详细介绍有关系统性红斑狼疮免疫发病机制的最新研究成果,重点关注生物通路的可变性以及对未来治疗策略的影响,尤其是嵌合抗原受体T(CAR T)细胞。
Immunopathogenesis of systemic lupus erythematosus: An update
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by dysregulated immune responses leading to widespread inflammation and damage in various organs. Environmental factors such as infections, hormonal influences and exposure to ultraviolet light can trigger the disease in genetically predisposed individuals. Genome-wide association studies have identified over 100 susceptibility loci linked to immune regulation, interferon (IFN) signaling and antigen presentation in SLE. In addition, rare cases of monogenic lupus have been instrumental in understanding critical underlying disease mechanisms. Several immunological abnormalities contribute to the loss of self-tolerance and the perpetuation of autoimmune responses in SLE. In particular, defective clearance of apoptotic cells due to defective phagocytosis and complement activation leads to accumulation of self-antigens. Dysregulated innate immune responses activate the adaptive immune system, amplifying the inflammatory response with an important role for type I IFNs. Abnormalities in B cell development and activation lead to the production of autoreactive antibodies, forming immune complexes that cause tissue damage. Similarly, disturbances in T-cell compartments, altered regulatory T-cell functions and altered cytokine production, particularly IFN-α, contribute to tissue damage. Understanding of the immunopathogenesis of SLE is evolving rapidly, with ongoing research identifying new molecular pathways and potential therapeutic targets. Future classifications of SLE are likely to be based on underlying biological pathways rather than clinical and serological signs alone. This review aims to provide a detailed update on the most recent findings regarding the immunopathogenesis of SLE, focusing on the variability of biological pathways and the implications for future therapeutic strategies, in particular chimeric antigen receptor T (CAR T) cells.
期刊介绍:
Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers.
The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences.
In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations.
Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.