Kidney Biopsy is a Sensitive Tool for Retrospective Diagnosis of PLA2R-related Membranous Nephropathy

Background: Antibodies against M-type phospholipase A2 receptor (PLA2R) are serological markers of disease activity in patients with idiopathic membranous nephropathy (iMN). To determine the most sensitive test for the diagnosis of PLA2R-related membranous nephropathy (MN) irrespective of sampling time, we investigated the presence of PLA2R in glomerular immune deposits and assessed circulating anti-PLA2R antibodies in a retrospective cohort of Czech patients with idiopathic, lupus and other few secondary MN.

Methods: We tested archival paraffin-embedded kidney biopsies of 84 consecutive patients with biopsy-proven MN, for the presence of PLA2R in glomerular immune deposits and we measured circulating anti-PLA2R antibodies using the indirect immunofluorescence test, all reagents being commercially available.

Results: In 45 of 65 (69%) patients with iMN, PLA2R was detected in a finely granular pattern in sub-epithelial deposits along glomerular capillary loops. Circulating anti-PLA2R antibodies were detected in 20 of 31 (65%) sera from patients sampled during active disease. Six patients with active disease were negative for circulating anti-PLA2R antibodies despite PLA2R antigen positivity in the kidney biopsies. Only 8 of 37 (22%) sera sampled at the time of remission were PLA2R positive while PLA2R antigen was found in 22 of the 37 (59%) corresponding biopsies. PLA2R was found in immune deposits in 3 patients with secondary MN (2 with hepatitis B, and 1 with sarcoidosis) but in none of the 16 patients with lupus.

Conclusions: In case of delayed serum sampling, assessment of PLA2R antigen in biopsy specimens is more sensitive than the serological test for the diagnosis of PLA2R-related MN which can be established retrospectively.