IgG型抗双链DNA抗体的产生机制与致病性研究

Production of anti-double-stranded DNA IgG and its pathogenicity

IgG 型抗双链 DNA 抗体是诊断系统性红斑狼疮(SLE)的重要自身抗体之一。该抗体的产生过程受紫外线、微生物感染等外源性诱导因素和自身基因易感性机制的调控,细菌 DNA 中高度保守的CpG 序列在抗双链 DNA 抗体产生过程中起免疫佐剂的作用,且该过程需要 Toll 样受体9(TLR9)与IL-10等因素的参与。IgG 型抗双链 DNA 抗体与狼疮肾炎关系非常密切,通过与肾脏固有细胞表面的某些靶抗原如α辅肌动蛋白等发生交叉结合可能是其致病机制之一。但抗双链 DNA 抗体阴性患者也可出现特异性肾脏损害,提示双链 DNA 可能并非激活抗体反应的唯一抗原。

IgG subtype of anti-double-stranded DNA （dsDNA） antibody has great value for the diagnosis of systemic lupus erythematosus （SLE）. The production of anti-dsDNA IgG is controlled by exogenous factors such as ultraviolet radiation, microbial infection, and so on. The genetic susceptibility of SLE patients plays a critical role as an endogenous effect. It has been known that bacterial CpG sequence has an important role in anti-dsDNA antibody production as immune adjuvant, which requires Toll-like receptor 9 and interleukin- 10. The anti-dsDNA antibody levels are directly correlated with the risk of lupus nephritis （LN）. The cross- reaction of anti-dsDNA IgG and alpha-actinin is pathogenic and may contribute to LN. Meanwhile the non- DNA antigens may also activate the immune response for the same renal damages in those patients without anti-dsDNA IgG.