Real-World Utility of Immunoglobulin G4 Subtype Phospholipase A2 Receptor Autoantibodies in Diagnosing Phospholipase A2 Receptor–Associated Membranous Nephropathy

Context.—: The role of anti-phospholipase A2 receptor (PLA2R) antibody (PLA2R-immunoglobulin [Ig] G) in management of membranous nephropathy (MN) is important. However, information regarding the value of its main subtype, PLA2R-IgG4, is limited. Objective.—: To evaluate the diagnostic value and clinical significance of serum and urine PLA2R-IgG4 in MN. Design.—: Patients with biopsy-confirmed MN and other glomerulopathies were enrolled. PLA2R-IgG and PLA2R-IgG4 were measured. Diagnostic performance and clinical significance were further analyzed. Results.—: A total of 406 patients were enrolled. The areas under the receiver operating characteristic curve (AUC) for serum PLA2R-IgG detected by enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay were comparable and demonstrated good agreement. The AUC for serum PLA2R-IgG4 was 0.853. At a cutoff of 147.51 ng/mL, sensitivity was 66.45%, which was higher than that for PLA2R-IgG detected by enzyme-linked immunosorbent assay (46.77%) and for PLA2R-IgG detected by time-resolved fluoroimmunoassay (51.95%). Serum PLA2R-IgG4 was correlated inversely with albumin (r = -0.39, P < .001), and positively with creatinine (r = 0.20, P < .001) and proteinuria (r = 0.33, P < .001). The AUC for urine PLA2R-IgG4/Cr was 0.754. Urine PLA2R-IgG4/Cr showed positive correlation with 24-hour proteinuria (r = 0.50, P < .001) and negative correlations with serum albumin (r = -0.58, P < .001) and serum creatinine (r = -0.27, P < .001). In patients presenting with nephrotic syndrome, the urine PLA2R-IgG4/Cr showed an equal diagnostic performance to that of serum PLA2R-IgG4 (AUC = 0.916 versus 0.940, P = .24). Conclusions.—: Serum PLA2R-IgG4 further enhanced diagnostic sensitivity. Urine PLA2R-IgG4 had an excellent diagnostic performance in patients with nephrotic syndrome and demonstrated superior correlation with clinical disease activity.