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 immuno fluorescence testing (IIFT) and ELISA. We assessed agreement between tests and correlated antibody titer with clinical baseline parameters and outcome. In this cohort, aPLA 2R 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 signi ficantly 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; P<0.01). IgG4 was the dominant subclass in the majority of patients. Titers of IgG4, but not IgG1 or IgG3, significantly correlated with the occurrence of spontaneous remission (P=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. Copyright © 2012 by the American Society of Nephrology.