Nature and functions of autoantibodies.
Nature and functions of autoantibodies.
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DOI：
10.1038/ncprheum0895
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Casali, Paolo
中科院分区：
文献类型：
--
作者：
Elkon, Keith;Casali, Paolo
与自身分子反应的抗体出现在健康个体中，被称为天然抗体或自身抗体。天然自身抗体主要是 IgM，由未突变的 V(D)J 基因编码，对自身抗原表现出中等亲和力。它们提供了抵御感染的第一道防线，可能具有内务功能并有助于免疫系统的稳态。相比之下，高亲和力、体细胞突变的 IgG 自身抗体反映了一种病理过程，其中与细胞清除、抗原受体信号传导或细胞效应功能相关的稳态途径受到干扰。在某些自身免疫性疾病中，自身抗体可能在疾病发作前就存在，表现出显着的特异性，并作为生物标志物，为诊断和治疗干预提供了机会。在重症肌无力或天疱疮等器官特异性自身免疫性疾病中，自身抗体直接结合并损伤靶器官。在系统性自身免疫性疾病中，自身抗体与游离分子（例如磷脂）以及细胞表面和核蛋白抗原发生反应，形成致病性抗原-抗体（免疫）复合物。这些自身抗体通过参与补体的 FcγR 激活以及 Toll 样受体的内化和激活来损伤组织和器官。浆细胞样树突状细胞中细胞内Toll样受体的激活导致I型干扰素的产生，而抗原呈递细胞上细胞内Toll样受体的结合刺激细胞激活和其他炎症细胞因子的产生。因此，免疫复合物可能会维持一个放大炎症反应的正反馈循环。
Antibodies that react with self-molecules occur in healthy individuals and are referred to as natural antibodies or autoantibodies. Natural autoantibodies are mainly IgM, are encoded by unmutated V(D)J genes and display a moderate affinity for self-antigens. They provide a first line of defense against infections, probably serve housekeeping functions and contribute to the homeostasis of the immune system. By contrast, high-affinity, somatically mutated IgG autoantibodies reflect a pathologic process whereby homeostatic pathways related to cell clearance, antigen-receptor signaling or cell effector functions are disturbed. In some autoimmune disorders, autoantibodies might be present before disease onset, show remarkable specificity and serve as biomarkers providing an opportunity for diagnosis and therapeutic intervention. In organ-specific autoimmune diseases, such as myasthenia gravis or pemphigus, autoantibodies directly bind to and injure target organs. In systemic autoimmune diseases, autoantibodies react with free molecules, such as phospholipids, as well as cell surface and nucleoprotein antigens, forming pathogenic antigen–antibody (immune) complexes. These autoantibodies injure tissues and organs through engagement of FcγR activation of complement as well as internalization and activation of Toll-like receptors. Activation of intracellular Toll-like receptors in plasmacytoid dendritic cells leads to the production of type I interferon, whereas engagement of intracellular Toll-like receptors on antigen-presenting cells stimulates cell activation and the production of other inflammatory cytokines. Thus, immune complexes might perpetuate a positive feedback loop amplifying inflammatory responses.
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