Anti-PLA2R1 antibodies in membranous nephropathy: do we have the smoking gun?

The discovery of anti–phospholipase A2 receptor 1 (PLA2R1) IgG4 in >70% of patients with membranous nephropathy (MN) represents one of the most significant advancements in our understanding of disease pathophysiology.1 However, the lack of PLA2R1 expression in rodents has prevented a clear understanding of the mechanisms responsible for antibody generation and their effector mechanisms. Despite compelling associative evidence supporting a relationship between anti-PLA2R1 IgG4 levels and human disease activity, no formal evidence exists that they are pathogenic.