Exploring PLA2R and HLA in membranous nephropathy: A narrative review of pathogenic mechanisms and emerging therapeutic potentials

Membranous Nephropathy (MN), a non-inflammatory autoimmune glomerulopathy, is a prominent cause of nephrotic syndrome, predominantly affecting Caucasian adults. It is characterized by significant thickening of the glomerular basement membrane, a direct result of immune complex deposition. Fundamental to its pathogenesis are the Phospholipase A2 receptor (PLA2R) and Human Leukocyte Antigens (HLA), which play crucial and interconnected roles. Specifically, PLA2R serves as the primary antigen, while HLA molecules facilitate MN-specific immune responses, thereby providing key insights into the disease's etiology. This study critically examines the roles of PLA2R and HLA in MN, with a particular focus on the antigenic epitopes of PLA2R. Given MN's complex nature, personalized therapeutic interventions are essential. Accordingly, targeting immunogenic epitopes has emerged as a transformative approach, aimed at modulating specific immune responses without disrupting overall immune function. Numerous studies and clinical trials have been advancing the application of these epitopes in therapeutic strategies. Nevertheless, challenges such as identifying effective epitopes, enhancing epitope-specific responses, and optimizing therapeutic dosing remain. This narrative review addresses these challenges in depth, offering a comprehensive insight into the pathology and emerging treatment strategies for MN.