Idiopathic nephrotic syndrome, the most common glomerular disorder in children, has long been considered an immune-mediated disease based on the efficacy of glucocorticoids at inducing remission. Nevertheless, the immune processes leading to podocytopathy have largely remained elusive. The success of B-cell depletion with rituximab, descriptions of B-cell dysregulation during active disease, and the most recent discovery of autoantibodies targeting the major podocyte antigen nephrin point to an autoimmune humoral etiology for idiopathic nephrotic syndrome. Investigations of the immune factors involved in idiopathic nephrotic syndrome pathogenesis have uncovered common features with other autoimmune disorders that will aid in prognostication and in guiding the expansion of our glucocorticoid-sparing therapeutic arsenal. In this review, we discuss the emerging autoimmune architecture of idiopathic nephrotic syndrome, with a specific focus on pediatric steroid-sensitive disease, including the podocyte-reactive B-cell response that causes anti-podocyte antibodies, the predisposing genetic factors that shape the podocyte-reactive immune landscape, and the immune triggers driving active disease.

中文翻译：

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儿童特发性肾病综合征的自身免疫结构


特发性肾病综合征是儿童中最常见的肾小球疾病，长期以来，基于糖皮质激素诱导缓解的疗效，一直被认为是一种免疫介导的疾病。然而，导致足细胞病的免疫过程在很大程度上仍然难以捉摸。利妥昔单抗成功去除 B 细胞，活动性疾病期间 B 细胞失调的描述，以及最近发现的靶向主要足细胞抗原肾蛋白的自身抗体，都指向特发性肾病综合征的自身免疫性体液病因。对特发性肾病综合征发病机制所涉及的免疫因子的调查发现了与其他自身免疫性疾病的共同特征，这些特征将有助于预后和指导我们糖皮质激素减量治疗库的扩展。在这篇综述中，我们讨论了特发性肾病综合征的新兴自身免疫结构，特别关注儿科类固醇敏感疾病，包括导致抗足细胞抗体的足细胞反应性 B 细胞反应、塑造足细胞反应性免疫景观的易感遗传因素，以及驱动活动性疾病的免疫触发因素。