Liang Wei, Zhang Hua, Wu Yi, Lai Zhiwei, Zhang Weiqiang, Cao Yuhao, Tan Lishan, Xiong Zibo, Yang Guang, Xiong Zuying
Department of Nephrology, School of Clinical Medicine, Peking University Shenzhen Hospital, Anhui Medical University, Shenzhen, Guangdong, 518036, People's Republic of China.
Division of Renal Medicine, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, People's Republic of China.
Int J Nephrol Renovasc Dis. 2025 Jun 9;18:163-175. doi: 10.2147/IJNRD.S523129. eCollection 2025.
Phospholipase A2 receptor 1 (PLA2R1) is often overexpressed in 70% of primary membranous nephropathy (PMN) patients, with serum PLA2R1 antibodies and podocyte PLA2R1 antigens serving as key diagnostic markers. However, a minority of patients test positive for only the PLA2R1 antigen and negative for PLA2R1 antibodies, presenting distinct characteristics. This study investigated the underlying features and mechanisms in PLA2R1 antigen-positive PMN patients.
26 patients' information was screened for analysis. And the effects of PLA2R1 overexpression on human podocytes (HPCs) was studied through cell experiments.
Clinical observations revealed that the median age of the 26 patients was 48.5 years, and the median onset time was 135 days. There was a significant negative correlation between blood albumin and antigen intensity. Cell studies demonstrated that PLA2R1 overexpression inhibited the proliferation and viability of HPCs. RNA sequencing and FACS assays revealed that PLA2R1 overexpression arrests HPCs at the S and G2/M phases.
PLA2R1 overexpression affects the course of the PMN by inhibiting the podocyte cycle. This study suggests that PLA2R1-related PMN pathogenesis could involve an additional immune response, offering insights into PMN treatment development.
磷脂酶A2受体1（PLA2R1）在70%的原发性膜性肾病（PMN）患者中常过度表达，血清PLA2R1抗体和足细胞PLA2R1抗原是关键诊断标志物。然而，少数患者仅PLA2R1抗原检测呈阳性而PLA2R1抗体检测呈阴性，表现出独特特征。本研究调查了PLA2R1抗原阳性PMN患者的潜在特征和机制。
筛选26例患者的信息进行分析。并通过细胞实验研究PLA2R1过表达对人足细胞（HPCs）的影响。
临床观察显示，26例患者的中位年龄为48.5岁，中位发病时间为135天。血白蛋白与抗原强度之间存在显著负相关。细胞研究表明，PLA2R1过表达抑制HPCs的增殖和活力。RNA测序和流式细胞术分析显示，PLA2R1过表达使HPCs停滞在S期和G2/M期。
PLA2R1过表达通过抑制足细胞周期影响PMN病程。本研究提示，PLA2R1相关的PMN发病机制可能涉及额外的免疫反应，为PMN治疗的发展提供了思路。
