Idiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity.
Idiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity.
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特发性膜性肾病：肾外免疫活性引起的肾小球病理模式
DOI：
10.3389/fimmu.2020.01846
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发表时间：
2020
影响因子：
7.3
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Liu W;Gao C;Liu Z;Dai H;Feng Z;Dong Z;Zheng Y;Gao Y;Tian X;Liu B
特发性膜性肾病（IMN）是由自身免疫反应引起的肾小球损伤的病理模式。免疫复合物沉积、肾小球基底膜厚度和足细胞形态学变化是导致蛋白尿发生的原因，蛋白尿是由自身抗体与足细胞靶向结合引起的。最近在IMN中鉴定了几种自身抗原，包括分泌型磷脂酶A2的M型受体（PLA 2 R1）、含血小板反应蛋白1型结构域的7A（THSD 7A）和神经表皮生长因子样蛋白1（NELL-1）。外周循环抗体的测定已成为临床重要的参考指标。然而，IMN的一些临床特征仍不清楚，需要进一步研究，如自身免疫启动，IgG 4优势，自发缓解，以及独特的肾小球病变。由于这些未解决的问题是密切相关的临床实践，我们提出了一个假设的发病机制模型的IMN。由环境刺激或其他原因诱导，暴露于肾外组织如肺的PLA 2 R1抗原和/或THSD 7A抗原然后产生靶向循环中的足细胞并对足细胞造成损伤的自身抗体。在这篇综述中，我们强调了环境刺激、免疫活性和肾小球病变之间的潜在联系，这是自发免疫和蛋白尿缓解的基础。
Idiopathic membranous nephropathy (IMN) is a pathological pattern of glomerular damage caused by an autoimmune response. Immune complex deposition, thickness of glomerular basement membrane, and changes in the podocyte morphology are responsible for the development of proteinuria, which is caused by the targeted binding of auto-antibodies to podocytes. Several auto-antigens have recently been identified in IMN, including M-type receptor for secretory phospholipase A2 (PLA2R1), thrombospondin type-1 domain-containing 7A (THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1). The measurement of peripheral circulating antibodies has become an important clinical reference index. However, some clinical features of IMN remain elusive and need to be further investigated, such as the autoimmunity initiation, IgG4 predominance, spontaneous remission, and the unique glomerular lesion. As these unresolved issues are closely related to clinical practice, we have proposed a hypothetical pathogenesis model of IMN. Induced by environmental stimuli or other causes, the PLA2R1 antigen and/or THSD7A antigen exposed to extrarenal tissues, such as lungs, then produce the auto-antibodies that target and cause damage to the podocytes in circulation. In this review, we highlighted the potential association between environmental stimuli, immune activity, and glomerular lesions, the underlying basis for spontaneous immune and proteinuria remission.
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