Contin-Bordes C, Lazaro E, Pellegrin J-L, Viallard J-F, Moreau J-F, Blanco P
CNRS UMR 5164, Université Bordeaux2,146 rue Léo Saignat, 33076 Bordeaux, France; Laboratoire d'immunologie, CHU de Bordeaux, Place Amélie Raba Léon 33076 Bordeaux cedex.
Rev Med Interne. 2009 Dec;30(12 Suppl):H9-13. doi: 10.1016/S0248-8663(09)73167-4.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiorgan involvement characterized by an immune response against nuclear components. SLE patients experience a waxing and waning disease course and exhibit a wide array of clinical manifestations, reflecting the systemic nature of the disease. Environmental triggers such as viruses are likely to act in the context of susceptibility genes, including genes involved in antigen/immune complex clearance, lymphoid signalling, or apoptosis, among several others, explaining why the pathogenesis of this disease remains largely uncovered. The abnormal activation of the innate immunity is central to SLE physiopathology. Dendritic cells activation and unabated secretion of IFN-alpha are the key features of the disease through their involvement in the capture and the presentation of nuclear material to the autoreactive adaptive arm (T and B lymphocytes) leading to the subsequent production of anti-nuclear autoantibodies. In this line, numerous studies have demonstrated the prominent role of immune complexes deposition throughout the body which directly can induce inflammation and tissue damage. However, animal models and recent human studies support the concept that other effector pathways including cytotoxic T-lymphocytes could be involved in SLE pathogenesis through their ability to migrate and/or target specifically different tissues. The aim of this review is not to provide a comprehensive review of the SLE pathophysiology but rather to give an overview of the immunological abnormalities associated to SLE. The treatments that are currently used or that are in development to fight against abnormal immune response in SLE will be detailed. The genetics of SLE is not the scope of this review.
系统性红斑狼疮(SLE)是一种累及多器官的系统性自身免疫性疾病,其特征为针对核成分的免疫反应。SLE患者经历病情的起伏过程,并表现出广泛的临床表现,这反映了该疾病的系统性本质。诸如病毒等环境触发因素可能在易感基因的背景下起作用,这些基因包括参与抗原/免疫复合物清除、淋巴细胞信号传导或细胞凋亡等的基因,这解释了为何该疾病的发病机制在很大程度上仍未明了。固有免疫的异常激活是SLE生理病理学的核心。树突状细胞的激活以及干扰素-α的持续分泌是该疾病的关键特征,因为它们参与了核物质的捕获和呈递给自身反应性适应性免疫分支(T和B淋巴细胞),进而导致抗核自身抗体的产生。在这方面,大量研究已证明免疫复合物在全身的沉积起着重要作用,其可直接诱导炎症和组织损伤。然而,动物模型和近期的人体研究支持这样一种概念,即包括细胞毒性T淋巴细胞在内的其他效应途径可能通过其迁移和/或特异性靶向不同组织的能力而参与SLE的发病机制。本综述的目的并非全面回顾SLE的病理生理学,而是概述与SLE相关的免疫异常情况。将详细介绍目前用于对抗SLE异常免疫反应的治疗方法以及正在研发的治疗方法。SLE的遗传学不在本综述范围内。