Validation of phospholipase A2 receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis

Abstract

Distinguishing between primary and secondary subtypes of membranous glomerulonephritis (MGN) is critical for its clinical management. We prospectively compared direct immunofluorescence (DIF) staining for phospholipase A₂ receptor (PLA₂R) on frozen renal biopsy with the presence of detectable serum PLA₂R antibody assessed by enzyme linked immunosorbent assay (ELISA) in the diagnosis of primary MGN. Forty-six patients with biopsy-proven MGN were enrolled from April 2017 to June 2019 with 31/46 (67.4%) being primary and 15/46 (32.6%) being secondary as determined by comprehensive clinical assessment. This is currently deemed to be the gold standard for distinguishing primary from secondary MGN. Amongst the 31 primary MGN patients, 24/31 were positive on PLA₂R DIF staining compared to 18/31 being positive on the PLA₂R ELISA (p=0.03). Amongst the 15 secondary MGN patients, 1/15 was positive on PLA₂R DIF compared to 0/15 on PLA₂R ELISA (p=1.0). In conclusion, the presence of PLA₂R staining on DIF demonstrated superior sensitivity and similar specificity compared to the detection of circulating PLA₂R antibodies by ELISA in the diagnosis of primary MGN in a cohort of 46 patients with biopsy-proven MGN. We suggest that DIF should be considered as part of routine work-up in all newly diagnosed cases of MGN.

Keywords: Phospholipase A(2) receptor antibody; direct immunofluorescence; frozen renal tissue; membranous glomerulonephritis; membranous nephropathy; phospholipase A(2) receptor staining.