Fig. 2.

Hypothesis for the pathogenesis of IgA nephropathy. Synthesis of IgA1 with some O-glycans deficient in galactose (autoantigen) is elevated. Gd-IgA1 is present in the circulation at increased levels (Hit 1). This immunoglobulin is recognized by unique circulating anti-glycan autoantibodies (Hit 2). This process results in the formation of pathogenic IgA1-containing circulating immune complexes (Hit 3), some of which deposit in the glomeruli and induce renal injury (Hit 4). Upstream factors are likely involved in abnormal mucosal/innate immune responses characteristic for patients with IgA nephropathy