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Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy
Barbora Svobodova1, Eva Honsova, Pierre Ronco
1Department of Nephrology, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
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.
Insights
Detecting phospholipase A2 receptor (PLA2R) antigen in kidney biopsies is more sensitive than serological tests for diagnosing PLA2R-related membranous nephropathy, especially with delayed serum samples.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Antibodies against M-type phospholipase A2 receptor (PLA2R) are key serological markers for idiopathic membranous nephropathy (iMN) disease activity.
- Diagnosis of PLA2R-related membranous nephropathy (MN) relies on identifying these antibodies or the antigen.
Purpose of the Study:
- To determine the most sensitive diagnostic test for PLA2R-related MN, irrespective of sample timing.
- To compare the sensitivity of detecting circulating anti-PLA2R antibodies versus PLA2R antigen in kidney biopsies.
Main Methods:
- Retrospective analysis of 84 Czech patients with biopsy-proven MN (idiopathic, lupus, secondary).
- Tested archival kidney biopsies for glomerular PLA2R immune deposits.
- Measured circulating anti-PLA2R antibodies using indirect immunofluorescence.
Main Results:
- PLA2R antigen detected in 69% of iMN kidney biopsies.
- Circulating anti-PLA2R antibodies found in 65% of active disease sera, but 6 patients were negative despite biopsy positivity.
- PLA2R antigen was detected in biopsies more frequently (59%) than antibodies (22%) in remission sera.
Conclusions:
- In cases of delayed serum sampling, PLA2R antigen assessment in kidney biopsies is more sensitive for diagnosing PLA2R-related MN.
- Kidney biopsy analysis allows for retrospective diagnosis of PLA2R-related MN when serological tests are negative.
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