Sialylated therapeutic IgG: a sweet remedy for inflammatory diseases?

Immunoglobulin G (IgG) is the main serum glycoprotein responsible for detection and destruction of pathogens or their noxious products. IgG consists of Fab (‘fragment antigen binding’) regions, that recognize antigenic targets and provide diversity to antibodies, and Fc (‘fragment crystallizable’) regions, that allow antibodies to interact with Fc gamma receptors (FcgR) on phagocytes (Fig. 1). Currently, four classes of FcgR are identified: FcgRI, FcgRII, FcgRIII and FcgRIV [1]. For the initiation of a biological response against the bound antigen, IgGs rely on their constant Fc portion. CH2 domains of the Fc fragment contain complex oligosaccharide structures covalently attached to asparagine 297 of the heavy chain of the IgG [2,3]. The presence of a complex oligosaccharide structure modulates the functions of IgG, especially the activation of complement and binding to FcgR [4]. The monosaccharide content of the complex oligosaccharides in antibodies, including monoclonal IgGs (MAbs), is highly variable. More than 30 different glycoforms linked to Fc have been described [4]. The impact of the carbohydrate structure on the biological functions of IgGs remains unresolved. Overview of the study by Kaneko et al. [5]