Abstract: TH-PO0669
Anti-Phospholipase A2 Receptor Antibodies Contribute to Hypercoagulation of Membranous Nephropathy by Promoting Pyroptosis of Endothelial Cells Through Fc-Gamma Receptor 1 (FcγRI)
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Ma, Qiqi, Peking University First Hospital, Beijing, China
- Lin, Caixia, Peking University First Hospital, Beijing, China
- Xu, Gaosi, Nanchang University Second Affiliated Hospital, Nanchang, Jiangxi, China
- Cui, Zhao, Peking University First Hospital, Beijing, China
- Zhao, Minghui, Peking University First Hospital, Beijing, China
Background
Thromboembolism, a severe complication of nephrotic syndrome, occurs disproportionately in membranous nephropathy (MN) compared to other pathological forms, suggesting disease-specific mechanisms beyond traditional risk factors such as proteinuria and hypoalbuminemia. The precise role of anti-phospholipase A2 receptor (PLA2R) antibodies and complement activation in endothelial dysfunction and thrombosis remains unclear.
Methods
The effects of MN plasma, anti-PLA2R IgG, and complement on human umbilical vein endothelial cells (HUVECs) were evaluated, focusing on pro- and anti-coagulant factor expression, pyroptosis pathways, and signaling mediated by Fc and complement receptors.
Results
We found that anti-PLA2R IgG induced a pro-coagulant phenotype in endothelial cells by upregulating tissue factor (TF) and ICAM-1 expression. FcγRI colocalized with anti-PLA2R IgG on endothelial cells, and its knockdown reversed the pro-coagulant effects by reducing caspase-1 activity, GSDMD-N expression, and the release of IL-1β and IL-18 . Additionally, C3a and C5a promoted pro-coagulant factor expression through their respective receptors.
Conclusion
These findings highlight the role of anti-PLA2R antibodies in endothelial dysfunction and thrombotic risk in MN, mediated by FcγRI-induced pyroptosis and pro-coagulant state, with complement activation serving as an additional contributor. Targeting these pathways may offer potential therapeutic strategies for mitigating thromboembolic complications in MN patients.