The discovery of phospholipase A2 receptor (PLA2R) as the primary target antigen in primary membranous nephropathy (MN) by Beck et al. (New England Journal of Medicine, 2009) transformed the clinical understanding and management of this condition. Circulating anti-PLA2R antibodies are detectable in approximately 70 to 80 percent of patients with primary MN, with high specificity for distinguishing primary from secondary forms, enabling serological diagnosis and therapeutic monitoring without repeated invasive biopsy.
The International Society of Nephrology has disseminated information on anti-PLA2R antibody testing through the KDIGO Clinical Practice Guidelines for Glomerulonephritis (2012 and 2021 update, Rovin et al., Kidney International), which incorporated anti-PLA2R serology into the diagnostic and monitoring algorithm for MN. ISN-affiliated nephrologists contributed substantially to the evidence base summarized in these guidelines.
Anti-PLA2R antibody titer monitoring as a surrogate for disease activity was prospectively validated by Ruggenenti et al. (Journal of the American Society of Nephrology, 2015), demonstrating that serological remission preceded clinical proteinuria remission by a median of 8.6 months and that persistent antibody positivity predicted relapse after cessation of immunosuppressive therapy. This finding rationalized the use of serial antibody monitoring in treatment decision algorithms.
Following the identification of PLA2R, additional target antigens in PLA2R-negative primary MN have been discovered. Tomas et al. (New England Journal of Medicine, 2014) identified THSD7A as a second major antigen, associated with higher prevalence of underlying malignancy. More recently, NELL-1, PCDH7, SEMA3B, and other antigens have been described by Sethi and colleagues (Kidney International, 2020–2023), establishing that primary MN encompasses a heterogeneous group of antigen-specific autoimmune glomerulopathies.
ISN has supported the growing role of B-cell-depleting therapies in MN management. The MENTOR trial (Fervenza et al., New England Journal of Medicine, 2019) demonstrated that rituximab was superior to cyclosporine in achieving complete or partial proteinuria remission at 24 months and in maintaining remission after therapy withdrawal, establishing rituximab as a preferred first-line immunosuppressive agent for primary MN in current ISN-aligned practice guidelines.