**4.2 The IgG glycosylation pattern**

All IgG molecules are glycoproteins with an N-glycosylated carbohydrate side chain that is important for antibody function [52]. Deletion of this carbohydrate (sugar) side chain results in poor binding to FcγRs [53]. The N-glycans are heterogeneous in their sugar composition and are attached to asparagine 297 (Asp297) in the Fc portion of the IgG [54]. The carbohydrate side chain may contain sugar residues such as galactose, fucose, and sialic acid in straight or branching patterns [46], and the differences in the glycosylation pattern seem to regulate IgG activity [55].

Many IgG antibodies present a fucose residue linked to an N-acetylglucosamine residue [56]. When this residue is removed, IgG molecules present an increased affinity to the FcγRIIIa [57], and also an increase in antibody-dependent cell cytotoxicity (ADCC) activity against various tumor cells [51, 57, 58]. Based on these findings, recombinant IgG antibodies with low fucose levels have been produced in order to increase their ADCC activity. Several of these antibodies are now in clinical trials to test their therapeutic potential [59].

Many IgG antibodies also present a carbohydrate side chain that terminates with sialic acid residues [60]. Contrary to antibodies without fucose, terminal sialic acid usually correlates with low affinity for FcγRs and also with lower ADCC activity [61, 62]. Interestingly, these sialic acid-rich antibodies seem to preferentially bind other receptors different from FcγRs. The receptor dendritic cell specific ICAM-3 grabbing nonintegrin (DC-SIGN) was identified as a receptor for sialic acid-rich IgG [63]. Therefore, terminal sialic acid can modify IgG activity by promoting less binding to FcγRs and more binding to other receptors [45].
