Early kinetics of anti-PLA2R-IgG4 predicts rituximab response in membranous nephropathy: a prospective biomarker study

While anti-PLA2R-IgG4 is a key biomarker in idiopathic membranous nephropathy (IMN), the predictive value of its early kinetics for rituximab (RTX) response is unclear. This prospective study enrolled 60 biopsy-proven IMN patients receiving RTX monotherapy. Serum anti-PLA2R-IgG and IgG4 were measured serially via time-resolved fluorescence immunoassay (TRFIA) over 12 months. The primary endpoint was clinical remission at 12 months. A rapid early decline in anti-PLA2R-IgG4 was the strongest predictor of remission. Patients achieving a ≥ 50% reduction in anti-PLA2R-IgG4 by month 1 (Rapid Decliners) had a significantly shorter median time to remission and a 4.91-fold higher likelihood of achieving remission compared to Slow Decliners. In contrast, early declines in total anti-PLA2R-IgG were not predictive. Multivariate analysis confirmed that the percentage decline in IgG4 at months 1, 2, and 4 were independent predictors of remission, with the model at month 4 showing the highest discriminative ability. When these kinetic indicators were included, baseline IgG4 level lost its independent predictive significance. The early kinetics of anti-PLA2R-IgG4 effectively predict the response to rituximab in membranous nephropathy, outperforming both baseline anti-PLA2R-IgG4 levels and total anti-PLA2R-IgG dynamics. Kewords. Anti-PLA2R-IgG4. Membranous nephropathy. Nephrotic syndrome. Prediction. Rituximab.