GalNAc-T14-associated defects in B cell homing in IgA nephropathy

IgA nephropathy (IgAN) is a common form of glomerulonephritis. Its pathogenesis has been linked to aberrant O-glycosylation of the IgA1 hinge region, which is thought to underlie the formation of IgA1-containing immune complexes that deposit in glomeruli. New insights suggest that IgA O-glycosylation may also affect additional processes, including mucosal immunity and B cell homing to mucosal and non-mucosal lymphoid tissues.

Sindhuri Prakash and colleagues initiated their study by identifying independent loss-of-function variants in an N-acetylgalactosaminyltransferase 14 (GalNAc-T14)-encoding gene, GALNT14, in a family segregating with IgAN (two people with biopsy-proven IgAN, one with IgA vasculitis and others with haematuria) and one individual with sporadic IgAN. Acetylgalactosaminyltransferases are enzymes that initiate the first step in the O-glycosylation of IgAN, suggesting a pathogenic role for the identified variants.