Table_1_Common Denominators in the Immunobiology of IgG4 Autoimmune Diseases: What Do Glomerulonephritis, Pemphigus Vulgaris, Myasthenia Gravis, Thrombotic Thrombocytopenic Purpura and Autoimmune Encephalitis Have in Common?.docx

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID.

IgG4自身免疫性疾病（IgG4-AID）是一类由IgG4亚类致病性自身抗体引起的新兴自身免疫性疾病。近期，人们才认识到，尽管受影响的抗原、组织及器官各不相同——如肾小球肾炎（肾脏）、天疱疮（皮肤）、血栓性血小板减少性紫癜（血液系统）、重症肌无力中的肌肉特异性激酶（MuSK）（周围神经系统）以及自身免疫性脑炎（中枢神经系统）等，该类疾病的成员仍共享相关的免疫生物学和治疗学特性。在这些疾病中，患者的IgG4亚类自身抗体阻断蛋白质-蛋白质相互作用，而非引起补体介导的组织损伤，患者对利妥昔单抗反应良好，并具有共同的遗传易感性：至少有五项个体研究报道，至少五种HLA II类基因与多种IgG4-AID相关联。这表明HLA II类区域，特别是DRβ1链，在异常启动针对慢性免疫反应的自身反应性T细胞，并偏向产生IgG4亚类自身抗体的过程中发挥着作用。本综述旨在提供关于IgG4-AID普遍存在的致病机制的最新发现，并就不同HLA单倍型、T细胞和细胞因子在IgG4-AID中的作用提出假设。