III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nat Rev Nephrol. 2022 Jul;18(7):466-478. doi: 10.1038/s41581-022-00564-1. Epub 2022 Apr 28.
Membranous nephropathy (MN) is characterized histomorphologically by the presence of immune deposits in the subepithelial space of the glomerular filtration barrier; its clinical hallmarks are nephrotic range proteinuria with oedema. In patients with primary MN, autoimmunity is driven by circulating autoantibodies that bind to one or more antigens on the surface of glomerular podocytes. Compared with other autoimmune kidney diseases, the understanding of the pathogenesis of MN has substantially improved in the past decade, thanks to the discovery of pathogenic circulating autoantibodies against phospholipase A receptor 1 (PLAR1) and thrombospondin type 1 domain-containing protein 7A (THSD7A). The subsequent identification of more proteins associated with MN, some of which are also endogenous podocyte antigens, might further advance the clinical characterization of MN, including its diagnosis, treatment and prognosis. Insights from studies in patients with MN, combined with the development of novel in vivo and in vitro experimental models, have potential to improve the management of patients with MN. Characterizing the interaction between autoimmunity and local glomerular lesions provides an opportunity to develop more specific, pathogenesis-based treatments.
膜性肾病（MN）的组织形态学特征是肾小球滤过屏障的上皮下空间存在免疫沉积物；其临床特征是肾病范围内的蛋白尿伴水肿。在原发性 MN 患者中，自身免疫是由循环自身抗体驱动的，这些自身抗体结合到肾小球足细胞表面的一个或多个抗原上。与其他自身免疫性肾脏疾病相比，由于发现了针对磷脂酶 A 受体 1（PLAR1）和血栓反应蛋白 1 型结构域包含蛋白 7A（THSD7A）的致病性循环自身抗体，过去十年中对 MN 发病机制的认识有了实质性的提高。随后，更多与 MN 相关的蛋白被鉴定出来，其中一些也是内源性足细胞抗原，这可能会进一步推进 MN 的临床特征分析，包括其诊断、治疗和预后。来自 MN 患者研究的见解，结合新型体内和体外实验模型的发展，有可能改善 MN 患者的管理。阐明自身免疫与局部肾小球病变之间的相互作用，为开发更具特异性、基于发病机制的治疗方法提供了机会。
