Clinical outcomes of immunosuppressive therapy in patients with seronegative anti-PLA2R antibodies and PLA2R-related membranous nephropathy.

BACKGROUND

The study aims to investigate the impact of immunosuppressive therapy on clinical outcomes in patients with baseline negative PLA2R antibody, providing new therapeutic insights for this patient population.

METHODS

This study included 133 patients with positive histological PLA2R antigen and baseline serum anti-PLA2R antibody data. ELISA (enzyme-linked immunosorbent assay) was used to measure serum anti-PLA2R antibody levels. Renal biopsy specimens were analyzed by light microscopy, immunofluorescence, and electron microscopy.

RESULTS

Among the 133 patients, 84 (63.2%) were positive for serum antibodies (SAb +) and glomerular antigen (GAg +), while 49 (36.8%) were negative for serum antibodies (SAb-) but positive for glomerular antigen (GAg +). Compared with the Sab-/GAg + group, the SAb + /GAg + group exhibited more severe clinical features compared to the SAb-/GAg + group; however, there was no significant difference in the pathological characteristics between the two groups of patients. The complete remission (CR) rate was significantly higher in the SAb-/GAg + group (67.35% vs. 33.33%, P < 0.001), with higher CR rates at 12, 24, and 36 months. The SAb-/GAg + group also had a lower relapse rate than Sab + /GAg + (12.24% vs. 36.90%, P = 0.002). In the SAb-/GAg + group, 67.3% received conservative treatment, while 32.7% underwent immunotherapy. Patients receiving immunosuppressive therapy in the SAb-/GAg + group exhibited more severe proteinuria, more impaired renal function, and higher hyperlipidemia at baseline. Compared with conservative treatment, immunotherapy improved overall remission rates (100.00% vs. 75.76%, P = 0.041) in the SAb-/GAg + group. Cox regression analysis showed that immunotherapy significantly predicted urinary protein remission (HR 3.92, 95% CI 1.58-9.70, P = 0.003).

CONCLUSION

Immunosuppressive therapy in PLA2R-related membranous nephropathy patients with severe baseline clinical manifestations may help predict urine protein remission, even if they are serum anti-PLA2R antibody negative.