IgG glycosylation in autoimmune diseases

Immunoglobulin G (IgG) is the most abundant glycoprotein in human serum. All IgG subclasses have a single-conserved N-linked glycosylation site at Asn297 of the heavy chain and 10–30% of IgGs are N-glycosylated also in a Fab region. N-glycans of Fc are sialylated and fucosylated biantennary complex-type structures. Glycosylation plays a key role in antibody function, and IgG N-glycans are essential for the proper activity of the immune system. Fc glycans areimportant for IgG effector functions, whereas Fab oligosaccharides modulate antigen binding.Glycosylation changes of IgG are associated with the development of various human diseases,including autoimmune states. The modification of one sugar moiety in N-glycan structure mayresult in the stimulation or suppression of immune response. The lack of core fucose leads tothe enhancement of pro-inflammatory activity, whereas an increase of sialylation determinesimmunosuppressive properties of IgG. The contribution of IgG Fc glycosylation changes hasbeen demonstrated in the pathogenesis of rheumatoid arthritis, lupus erythematosus andCrohn’s disease. A decrease in IgG galactosylation and sialylation, found in these diseases,activates effector cells and triggers inflammatory reactions. A detailed analysis of changes inIgG glycosylation and their effects on the development of autoimmune diseases is importantin the treatment of these diseases. IgGs with modified α2,6-sialylation are used as therapeuticantibodies with anti-inflammatory properties. Numerous studies on IgG glycosylation haveprovided evidence of the role of this post-translational modification in the proper functioningof antibodies and the importance of changes in the structure of IgG glycans, mainly incompletegalactosylation and desialylation, in the pathogenesis of many diseases. The continuationof these studies may contribute to explaining the mechanisms of autoimmunity that is stillpoorly understood.