Serum Anti-PLA2R Antibody and Renal Complement Deposition: Associations with Clinicopathological Features in Primary Membranous Nephropathy

Abstract Background The pathogenic roles of serum anti-phospholipase A2 receptor (PLA2R) antibodies and complement deposition in renal tissue remain incompletely understood in primary membranous nephropathy (PMN). This study aimed to evaluate their prevalence and associations with clinicopathological features and renal prognosis. Methods A retrospective analysis was conducted in 302 biopsy-proven PMN patients, stratified into anti-PLA2R antibody-positive (≥ 20 IU/mL, n = 136) and -negative (< 20 IU/mL, n = 166) groups. Baseline clinical data, renal histopathology, and follow-up outcomes were analyzed. Multivariate logistic regression and Cox proportional hazards models were applied to identify independent predictors of non-remission and renal dysfunction. Results Compared to antibody-negative patients, those with anti-PLA2R positivity had significantly higher proteinuria and serum cholesterol levels, lower albumin and IgG levels, and a higher rate of glomerular IgG4 deposition (all P < 0.01). Among 225 patients with follow-up data, the antibody-positive group exhibited more frequent renal dysfunction and increased use of immunosuppressive therapy. Stronger C3 deposition in renal tissue was associated with lower serum albumin and C3 levels, higher anti-PLA2R antibody titers, and more glomerulosclerosis. Multivariate analyses identified hypoalbuminemia and glomerulosclerosis as independent predictors of non-remission, while older age and intense C3 deposition independently predicted renal dysfunction. Conclusions Anti-PLA2R antibody positivity and prominent C3 deposition are associated with more severe clinical presentation and poorer renal outcomes in PMN. These findings highlight their potential as prognostic biomarkers and therapeutic targets.