Serum anti-PLA2R negativity does not exclude glomerular PLA2R expression in primary membranous nephropathy.

Primary membranous nephropathy (pMN) is a principal cause of nephrotic syndrome in adults. The identification of the M-type phospholipase A2 receptor (PLA2R) antigen has significantly advanced non-invasive management; however, the precise clinical relationship between circulating antibody titers and intrarenal antigen deposition continues to be debated. This single-center retrospective study sought to analyze the correlation between clinicopathological parameters, serum anti-PLA2R levels, and glomerular PLA2R tissue expression in pMN. A specific focus was placed on evaluating the diagnostic utility of tissue staining in seronegative patients. A cohort of 49 adult pMN patients, diagnosed via renal biopsy between 2018 and 2025, was evaluated. Serum anti-PLA2R antibodies were quantified using ELISA, while glomerular PLA2R expression and staining intensity (graded 0 to +3) were assessed via immunohistochemistry (IHC) on paraffin-embedded sections. The results demonstrated a notable discordance: the overall serum antibody positivity rate was 49.0%, yet tissue PLA2R expression was detected in 100% of the cohort, encompassing all seronegative cases. A statistically significant difference was observed in the distribution of tissue PLA2R staining intensity based on serum PLA2R status (p=0.002). Conversely, no statistically significant correlation was found between circulating antibody titers and baseline renal function or proteinuria markers (p>0.05). In conclusion, these findings indicate that negative serology does not preclude tissue PLA2R positivity, potentially attributable to mechanisms such as the "kidney-as-a-sink" phenomenon or persistent immunological footprints. This investigation underscores that serum and tissue PLA2R serve as complementary, rather than mutually exclusive, markers. Consequently, renal biopsy with supplementary IHC staining remains a crucial and clinically valuable diagnostic tool, particularly in seronegative cases.