Long-term outcomes in primary membranous nephropathy: a Chinese cohort study with novel target antigen

Background Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. Methods We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010–2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated. Results PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, P = 0.003), with better renal function and more frequent C1q deposition (38.1% vs. 13.5%, P = 0.016). Serum anti-PLA2R antibodies were detected in 55.3% of patients and strongly correlated with tissue PLA2R positivity (AUC = 0.851; optimal cutoff ≥17.47 RU/mL). Baseline antibody titers were not associated with remission ( P = 0.573). During 5-years follow-up, 42.4% achieved CR, 36.4% PR, and 21.2% had NR, with an estimated 5-year renal survival rate of 81.95%. No malignancy events were observed among the seven THSD7A-positive patients or the single NELL-1–positive patient in this cohort. Statistical power for rare antigen subgroups was limited. Conclusions This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN.