Antiphospholipase A2 Receptor Antibody Titer and Subclass in Idiopathic Membranous Nephropathy

Abstract

The phospholipase A₂ receptor (PLA₂R) is the major target antigen in idiopathic membranous nephropathy. The technique for measuring antibodies against PLA₂R and the relationship between antibody titer and clinical characteristics are not well established. Here, we measured anti-PLA₂R (aPLA₂R) antibody titer and subclass in a well defined cohort of 117 Caucasian patients with idiopathic membranous nephropathy and nephrotic-range proteinuria using both indirect immunofluorescence testing (IIFT) and ELISA. We assessed agreement between tests and correlated antibody titer with clinical baseline parameters and outcome. In this cohort, aPLA₂R antibodies were positive in 74% and 72% of patients using IIFT and ELISA, respectively. Concordance between both tests was excellent (94% agreement, κ=0.85). Among 82 aPLA₂R-positive patients, antibody titer significantly correlated with baseline proteinuria (P=0.02). Spontaneous remissions occurred significantly less frequently among patients with high antibody titers (38% versus 4% in the lowest and highest tertiles, respectively; PP=0.03). In summary, these data show high agreement between IIFT and ELISA assessments of aPLA₂R antibody titer and highlight the pathogenetic role of these antibodies, especially the IgG4 subclass, given the observed relationships between aPLA₂R titer, baseline proteinuria, and outcome.