Levine J S, Koh J S
Department of Medicine, Boston Medical Center, MA 02118, USA.
Semin Nephrol. 1999 Jan;19(1):34-47.
The immunologic basis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) is complex and multifaceted. Recent advances in the field of apoptosis have suggested new paradigms for the development of autoimmunity. This review examines the role that apoptosis plays in maintaining immunologic tolerance to self-antigens, and how abnormalities in the regulation of apoptosis can lead to a breakdown in self-tolerance. This article also examines the increasing recognition of apoptotic cell antigens as the targets of autoantibodies and discusses the possibility that the autoimmune response characteristic of SLE is specifically directed against apoptotic cells. In addition, we will describe some of the features that distinguish nonpathogenic anti-DNA autoantibodies from those which deposit in the kidney and lead to lupus nephritis. Finally, we will attempt to synthesize the vast body of data connecting apoptosis and SLE into a single hypothesis in which we suggest that apoptotic cells are a primary source of immunogen, and that abnormalities in the handling of apoptotic cells can lead to a breakdown in self-tolerance.
系统性自身免疫性疾病，如系统性红斑狼疮（SLE）的免疫基础复杂且多方面。细胞凋亡领域的最新进展为自身免疫性疾病的发展提出了新的范例。本综述探讨了细胞凋亡在维持对自身抗原的免疫耐受中所起的作用，以及细胞凋亡调节异常如何导致自身耐受的破坏。本文还探讨了对凋亡细胞抗原作为自身抗体靶点的认识不断增加，并讨论了SLE的自身免疫反应特异性针对凋亡细胞的可能性。此外，我们将描述一些区分非致病性抗DNA自身抗体与那些沉积在肾脏并导致狼疮性肾炎的自身抗体的特征。最后，我们将尝试把大量将细胞凋亡与SLE联系起来的数据综合成一个单一的假说，在这个假说中，我们认为凋亡细胞是免疫原的主要来源，并且凋亡细胞处理过程中的异常会导致自身耐受的破坏。
