免疫学
肾病
免疫球蛋白A
抗体
肾小球肾炎
发病机制
同型
肾炎
分泌成分
补体系统
生物
免疫球蛋白G
医学
肾
单克隆抗体
内分泌学
糖尿病
作者
Yasunori Nihei,Hitoshi Suzuki,Yusuke Suzuki
标识
DOI:10.3389/fimmu.2023.1165394
摘要
Immunoglobulin A (IgA) is the most abundant isotype of antibodies, provides a first line of defense at mucosal surfaces against pathogens, and thereby contributes to mucosal homeostasis. IgA is generally considered as a non-inflammatory antibody because of its main function, neutralizing pathogenic virus or bacteria. Meanwhile, IgA can induce IgA-mediated diseases, such as IgA nephropathy (IgAN) and IgA vasculitis. IgAN is characterized by the deposition of IgA and complement C3, often with IgG and/or IgM, in the glomerular mesangial region, followed by mesangial cell proliferation and excessive synthesis of extracellular matrix in glomeruli. Almost half a century has passed since the first report of patients with IgAN; it remains debatable about the mechanism how IgA antibodies selectively bind to mesangial region—a hallmark of IgAN—and cause glomerular injuries in IgAN. Previous lectin- and mass-spectrometry-based analysis have revealed that IgAN patients showed elevated serum level of undergalactosylated IgA1 in O-linked glycans of its hinge region, called galactose-deficient IgA1 (Gd-IgA1). Thereafter, numerous studies have confirmed that the glomerular IgA from IgAN patients are enriched with Gd-IgA1; thus, the first hit of the current pathogenesis of IgAN has been considered to increase circulating levels of Gd-IgA1. Recent studies, however, demonstrated that this aberrant glycosylation alone is not sufficient to disease onset and progression, suggesting that several additional factors are required for the selective deposition of IgA in the mesangial region and induce nephritis. Herein, we discuss the current understanding of the characteristics of pathogenic IgA and its mechanism of inducing inflammation in IgAN.
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