A New Chemiluminescence Immunoassay For Phospholipase A(2) Receptor 1 Autoantibodies Allows Early Identification Of Autoantibody Recurrence In Patients With Membranous Nephropathy

Background: Circulating autoantibodies against the M-type phospholipase A2 receptor 1 (PLA(2)R1) are important biomarkers in membranous nephropathy (MN), supporting the diagnosis and the clinical monitoring of patients. Standardized recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA) are widely established for the detection of anti-PLA(2)R1 autoantibodies (PLA(2)R1-ab). The RC-IFA provides higher sensitivity than the ELISA, but lacks exact graduated quantification of antibody levels. In this study, we evaluated the diagnostic performance of a novel PLA(2)R1-ab immunoassay based on chemiluminescence (ChLIA) by comparing it to RC-IFA and ELISA in samples from patients with MN with different diagnostic scenarios.Methods: Serum samples from patients with biopsy-proven MN and disease controls were analyzed for PLA(2)R1-ab by ChLIA, ELISA, and RC-IFA.Results: The ChLIA demonstrated almost perfect agreement with RC-IFA for the identification of patients with PLA(2)R1-associated MN, while additionally allowing fine-graduated quantification of PLA(2)R1-ab levels. In patients with a relapse of MN, the ChLIA allowed an earlier detection of PLA(2)R1-ab recurrence by at least 3 months in 63% of cases compared with the ELISA.Conclusions: The PLA(2)R1-ab ChLIA had the same excellent diagnostic performance as the RC-IFA and outperformed the ELISA in the diagnosis of MN and the early identification of relapses. It thus presents a favorable tool for accurate PLA(2)R1-ab assessment in routine diagnostic settings, while enabling fast processing and fully automated random-access implementation.