The diagnostic and prognostic value of Anti PLA2R-Ab testing in Membranous Nephropathy

Abstract

Background: The identification of PLA2R1 antigen on glomeruli as the target for antibodies in Primary Membranous Nephropathy (PMN) has raised hopes for improved patient outcomes. However, variability exists in diagnostic methods and prognostic cut-off values for anti-PLA2R1 antibodies, necessitating standardization. Methods: A systematic review and meta-analysis assessed the diagnostic accuracy of anti-PLA2R-Ab test and other non-invasive biomarkers for distinguishing PMN, secondary membranous nephropathy (SMN), and other glomerulonephritis (GN). A single-center diagnostic accuracy study and multicenter retrospective study investigated diagnostic and prognostic utility. Cox-proportional hazard testing evaluated associations with outcomes. Results: In meta-analysis, EUROIMMUN ELISA at cut-offs of 10 and 20 RU/ml showed pooled sensitivity/specificity of 0.71/0.93 and 0.63/0.96, respectively. EUROIMMUN IF at 1:10 threshold had sensitivity/specificity of 0.705/0.99. The single-center study revealed a PPV of 97.3% and sensitivity of 75.5% for PLA2R-Ab, with a cut-off >20 RU/ml. In the multi-center prognostic study, eGFR and uPCR were associated with progression. Baseline PLA2R-Ab positivity or high titer did not affect progression or partial remission. Of 18 patients in the single-center prognostic study, 16 achieved partial remission, with 7 achieving complete remission. Two developed ESRD, while 4 experienced infections and cancer, resulting in 4 deaths. Conclusion: Anti-PLA2R-Ab test demonstrates high specificity for PMN diagnosis but lacks consistent prognostic value. Future research aims to elucidate alternative prognostic markers and develop a prognostic model based on common immune pathway signals.

Date of Award	11 Apr 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Sandip Mitra (Co Supervisor), Durga Kanigicherla (Main Supervisor) & Tracy Hussell (Co Supervisor)