Figure 1.

The galactose-deficient IgA1 molecule and the immune complexes formation in the pathogenesis of IgAN. IgA1 has characteristic hinge regions between the CH₁ and CH₂ domains (CH, the constant regions of the heavy chain), which contain at least six serine (Ser) or threonine (Thr) residues as O-linked glycosylation sites. In the first step, the enzyme polypeptide N-acetylgalactosaminyltransferase (pp-GalNAc-T2) facilitates the attachment of N-acetylgalactosamine (GalNAc) to these residues. In the second step, the IgA1 glycosylation is extended in two ways. One is the binding of N-acetylneuraminic acid (NeuNAc) to GalNAc through the action of the enzyme N-acetylgalactosamine-specific α2,6-sialyltransferas (ST6GalNAc2) [17]. The other is galactose (Gal) connection to GalNAc through the enzyme core 1 β1,3 galactosyltransferase (C1GalT1) and core-1-β3-Gal-T specific molecular chaperone (Cosmc) [18]. The imbalance between those activities may promote galactose-deficient IgA1 production [10, 18]. Galactose-deficient IgA1 is aggregated with antiglycan IgG or IgA1 antibodies, resulting in formation of immune complexes [13], which may escape the normal catabolism in liver and also accumulate with high affinity in glomerular mesangium.