Jacob L, Viard J P
INSERM U25, Hôpital Necker, Service de Médecine Interne A, Paris, France.
Eur J Med. 1992 Nov;1(7):425-31.
Systemic lupus erythematosus (SLE) is the archetypic non-organ specific autoimmune disease in which polyclonal B-cell activation is reflected by the wide range of auto-antibody specificities. Among these, anti-ds DNA antibodies bear special significance since they are disease specific, tend to occur at high titers in an active clinical state and are considered to be pathogenic through immune complex formation. However, data accumulated in the last few years have led to a somewhat more complex view of anti-DNA autoantibodies and SLE pathogenesis. For instance, the definition of pathogenic subpopulations of anti-DNA antibodies is an important question which has been addressed in terms of isotypes, idiotypes and DNA sequences of antibodies. Also, some of the cross reactivities described with monoclonal anti-DNA antibodies appear to be due to the formation of immune complexes with DNA, histones or nucleosomes. In addition, anti-DNA-nucleosome immune complexes can react with the cell membrane. These findings indicate that not only DNA but also the nucleosome as a multimolecular complex or its non-DNA component, i.e. histone, may be viewed as relevant target autoantigens in SLE. This review will focus on experimental data supporting this new representation of this set of autoantibodies directed against DNA, histone and the nucleosome, and their possible intervention in SLE pathogenesis.
系统性红斑狼疮（SLE）是典型的非器官特异性自身免疫性疾病，其中多克隆B细胞活化表现为多种自身抗体特异性。其中，抗双链DNA（dsDNA）抗体具有特殊意义，因为它们具有疾病特异性，在临床活动期往往以高滴度出现，并被认为通过免疫复合物形成而具有致病性。然而，过去几年积累的数据使人们对抗DNA自身抗体和SLE发病机制的看法变得更加复杂。例如，抗DNA抗体致病亚群的定义是一个重要问题，已经从抗体的同种型、独特型和DNA序列方面进行了探讨。此外，一些与单克隆抗DNA抗体相关的交叉反应似乎是由于与DNA、组蛋白或核小体形成免疫复合物所致。此外，抗DNA-核小体免疫复合物可与细胞膜发生反应。这些发现表明，不仅DNA，而且作为多分子复合物的核小体或其非DNA成分，即组蛋白，都可被视为SLE相关的靶自身抗原。本综述将重点关注支持针对DNA、组蛋白和核小体的这组自身抗体的新观点的实验数据，以及它们对SLE发病机制的可能干预。
