Beyond galactose-deficient IgA1: reconsidering IgA2 as a pathogenic driver in IgA nephropathy.

IgA nephropathy (IgAN) has long been viewed as a disease driven almost exclusively by IgA1, in particular galactose-deficient IgA1. However, emerging evidence challenges this IgA1-centric paradigm. In this issue of Kidney International, Li et al. demonstrate that IgA2 is consistently deposited in IgAN glomeruli and actively promotes complement activation, macrophage infiltration, and tubulointerstitial injury. These findings could redefine IgA2 from a passive bystander to a pathogenic amplifier, linking mucosal immunity, complement biology, and progression of kidney disease in IgAN.