Antiphospholipase A2 Receptor Autoantibodies: A Step Forward in the Management of Primary Membranous Nephropathy

Abstract

Since the identification of PLA2R (M-type phospholipase A2 receptor) as the first human antigenic target in primary membranous nephropathy (MN), perpetual progress has been made in understanding the pathogenesis of this disease. Accumulating clinical data support a pathogenic role for the anti-PLA2R antibodies (PLA2R ABs), but confirmation in an animal model is still lacking. However, PLA2R ABs were related to disease activity and outcome, as well as to response therapy. Accordingly, PLA2R ABs assay seems to be promising tool not only to diagnose MN but also to predict the course of the disease and could open the way to personalize therapy. Nevertheless, validation of a universal assay with high precision and definition of cut-off levels, followed by larger studies with a prolonged follow-up period, are needed to confirm these prospects.

Figure 1

Phospholipase A2 receptor (PLA2R), anti-PLA2R antibody (anti-PLA2R AB), and membranous nephropathy pathogenesis. GBM: glomerular basement membrane; ROS: reactive oxigen species.

Figure 2

Anti-PLA2R AB and proteinuria in patients with primary membranous nephropathy after rituximab administration (data from Beck et al. [40]).