Combined evaluation of glomerular phospholipase A2 receptor and immunoglobulin G subclass in membranous nephropathy

Abstract

Abstract Background Phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic membranous nephropathy (MN). Anti-PLA2R antibodies are mainly of immunoglobulin G (IgG) subclass IgG4, although other IgG subclass depositions in glomeruli also can be detected. However, the importance of the subclass of IgG deposit has not been proven. Thus, we investigated clinical findings from patients with idiopathic MN in relation to glomerular PLA2R deposition and IgG subclass. Methods We enrolled 132 Japanese patients with biopsy-proven idiopathic MN in a multicenter retrospective observational study. We investigated the complete remission rate as primary outcome and the development of end-stage kidney disease (ESKD) as secondary outcome in relation to glomerular PLA2R deposition. Moreover, we evaluated prognostic factors, including glomerular IgG subclass, in the PLA2R-positive group. Results The percentage of cases with glomerular PLA2R deposition was 76.5% (n = 101). The first complete remission rate of the PLA2R-positive group was worse than that of the PLA2R-negative group (log-rank test P < 0.001). ESKD incidence did not significantly differ between the glomerular PLA2R-negative and PLA2R-positive MN groups (log-rank test P = 0.608). In the PLA2R-positive group, higher PLA2R intensities and IgG2 staining were associated with a poorer first complete remission rate (log-rank test P < 0.001 and P = 0.032, respectively). Cox proportional hazards analysis also showed that strong PLA2R deposition and positive IgG2 staining were significantly associated with a failure to reach complete remission (hazard ratio: 2.09 [P = 0.004] and 1.78 [P = 0.030], respectively). Conclusions Our results suggest that intense glomerular PLA2R and IgG2 positivity predict a poor proteinuria remission rate in idiopathic MN.