Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy

Abstract

The phospholipase A(2) receptor (PLA(2)R) is the major target antigen in idiopathic membranous nephropathy. The technique for measuring antibodies against PLA(2)R and the relationship between antibody titer and clinical characteristics are not well established. Here, we measured anti-PLA(2)R (aPLA(2)R) 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, aPLA(2)R 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 aPLA(2)R-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; 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 aPLA(2)R antibody titer and highlight the pathogenetic role of these antibodies, especially the IgG4 subclass, given the observed relationships between aPLA(2)R titer, baseline proteinuria, and outcome.

Figure 1.

Correlation between anti-PLA₂R antibody levels measured with IIFT (titers: 1/10 to 1/3200) and ELISA (units per milliliter) techniques. There is a significant correlation (r=0.868, P<0.01), but large overlap.

Figure 2.

Correlation between anti-PLA₂R levels measured with an ELISA technique and proteinuria in patients of the Dutch cohort. (A) Unadjusted analysis. (B) Anti-PLA₂R levels adjusted for fractional excretion of IgG.

Figure 3.

Correlation between IgG4 anti-PLA₂R antibody levels and total IgG anti-PLA₂R (ELISA technique). IgG4 antibodies and total IgG antibodies were quantitated (see Concise Methods). There is a significant correlation (r=0.668, P<0.01).