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


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Yıldırim Ş., İNCİ A., Avcı A. K., Koç L. Z., Nergiz D., Yılmaz Ü.

Biomolecules and Biomedicine, vol.26, no.10, pp.1881-1890, 2026 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 26 Issue: 10
  • Publication Date: 2026
  • Doi Number: 10.17305/bb.2026.14167
  • Journal Name: Biomolecules and Biomedicine
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals, Biomedical Reference Collection: Corporate Edition (EBSCO)
  • Page Numbers: pp.1881-1890
  • Keywords: anti-PLA2R antibodies, glomerular PLA2R expression, kidney-as-a-sink hypothesis, Primary membranous nephropathy, renal biopsy
  • Open Archive Collection: AVESIS Open Access Collection
  • Akdeniz University Affiliated: Yes

Abstract

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 overaserum 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 anbaseline 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.