Antibodies to DNA: infection or genetics?
Antibodies to DNA: infection or genetics?
复制标题
DOI：
10.1177/0961203309106492
复制
发表时间：
2009-11-01
期刊：
影响因子：
2.6
通讯作者：
Vrabie, I. A.
中科院分区：
文献类型：
--
作者：
Pisetsky, D. S.;Vrabie, I. A.
抗DNA抗体(抗DNA)是系统性红斑狼疮(SLE)的血清学标志，也是疾病发病机制中至关重要的免疫紊乱的独特标志。以免疫复合体的形式，抗DNA自身抗体可以沉积在组织中，引发炎症和损害；此外，这些复合体可以诱导细胞因子的产生，最突出的是1型干扰素。在患者和动物模型中的研究表明，遗传和环境因素都与抗DNA反应的病因学有关。由于细菌DNA通过Toll样受体(TLR)和非TLR信号通路有效地刺激天然免疫，在细菌或病毒感染过程中引入的外来DNA可能在抗体诱导中具有双重作用。这种DNA可以作为一种佐剂来激活天然免疫，也可以作为一种免疫原来驱动抗原特异性抗体反应。在这种情况下，与针对细菌DNA的高度特异性抗体相比，交叉反应自身抗体的产生很可能取决于SLE患者B细胞谱系中由遗传决定的异常。鉴于DNA的普遍表达，该模型表明，许多不同类型的感染可以在SLE中触发病理性自身抗体反应，以及引发红斑狼疮。狼疮(2009)18,1176-1180。
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and unique markers of the immunological disturbances critical to disease pathogenesis. In the form of immune complexes, anti-DNA autoantibodies can deposit in the tissue to incite inflammation and damage; in addition, these complexes can induce cytokine production, most prominently, type 1 interferon. Studies in both patients and animal models have implicated genetic as well as environmental factors in the aetiology of the anti-DNA response. Because bacterial DNA is a potent stimulant of innate immunity by both toll-like receptor (TLR) and non-TLR signalling pathways, foreign DNA introduced during the course of bacterial or viral infection could have a dual role in antibody induction. This DNA could serve as an adjuvant to activate innate immunity as well as an immunogen to drive an antigen-specific antibody response. In this scenario, the generation of cross-reactive autoantibodies, in contrast to highly specific antibodies to bacterial DNA, most likely depends on genetically determined abnormalities in the B-cell repertoire in patients with SLE. Given the universal expression of DNA, this model suggests that many different kinds of infections could trigger pathogenic autoantibody responses in SLE, as well as induce flare. Lupus (2009) 18, 1176-1180.