White Sarah, Rosen Antony
Department of Medicine/Rheumatology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Curr Opin Rheumatol. 2003 Sep;15(5):557-62. doi: 10.1097/00002281-200309000-00006.
Systemic lupus erythematosus is a complex, multisystem autoimmune disease characterized by production of high-titer autoantibodies directed against ubiquitously expressed self-antigens. Autoantigens in systemic lupus erythematosus are highly diverse in terms of structure and location in control cells, but become clustered in and on the surface blebs of apoptotic cells. The past several years have provided significant evidence that the apoptotic cell plays a central role in tolerizing B cells and T cells to both tissue-specific and ubiquitously expressed self-antigens, and may drive the autoimmune response in systemic autoimmune disease. The authors review the significant recent advances in this area. Recent studies suggest that predisposing factors to subsequent development of systemic autoimmunity may be the incomplete induction of tolerance to apoptotic antigens, potentially through abnormal apoptotic signaling and effector pathways, decreased apoptotic cell clearance, or abnormal signaling thresholds on responding lymphocytes. In such genetically susceptible hosts, proinflammatory events at the host-environment-immune system interface that lead to the binary change in the response to apoptotic material from tolerance to immunity may be responsible for initiation of autoimmunity and subsequent disease amplification. Such pathways may be amenable to therapeutic and preventive interventions.
系统性红斑狼疮是一种复杂的多系统自身免疫性疾病，其特征是产生针对普遍表达的自身抗原的高滴度自身抗体。系统性红斑狼疮中的自身抗原在对照细胞中的结构和位置方面高度多样，但在凋亡细胞的表面小泡内和表面聚集。过去几年提供了重要证据，表明凋亡细胞在使B细胞和T细胞耐受组织特异性和普遍表达的自身抗原方面起核心作用，并可能在系统性自身免疫性疾病中驱动自身免疫反应。作者回顾了该领域最近的重大进展。最近的研究表明，随后发生系统性自身免疫的易感因素可能是对凋亡抗原的耐受性诱导不完全，这可能是通过异常的凋亡信号传导和效应途径、凋亡细胞清除减少或反应性淋巴细胞上的异常信号阈值导致的。在这种遗传易感宿主中，宿主-环境-免疫系统界面处导致对凋亡物质的反应从耐受转变为免疫的二元变化的促炎事件可能是自身免疫启动和随后疾病放大的原因。这些途径可能适合进行治疗和预防干预。
