O-Glycosylation pathways of the human IgA1 hinge region (HR). The biosynthesis process starts with the attachment of N-acetylgalactosamine (GalNAc) to Ser/Thr residues in the HR by UDP-GalNAc-transferase 2 (GalNAc-T2). GalNAc residues are extended by galactose or N-acetylneuraminic acid (NeuAc) by core 1 β1,3-galactosyltransferase (C1GalT1) and its molecular chaperone Cosmc or α2,6 sialyltransferase (ST6GalNAc2), respectively. Finally, the O-glycan structure is completed by attachment of NeuAc to the galactose residue and/or GalNAc residues, each of which is mediated by α2,3-sialyltransferase (ST3Gal1) and ST6GalNAc2. The sialylation of GalNAc before the attachment of galactose prevents galactosylation of GalNAc (marked by *) [62].