Antibody and Protein Glycosylation in Health and Disease

Publisher Summary This chapter focuses on the natural profile of glycoforms of protein molecules, particularly human IgG antibodies, and altered or abnormal glycoforms associated with disease. Glycosylation of protein molecules represents an extensive post-translational modification that can influence biological activity, pharmokinetics, and antigenicity. Glycosylation may occur through attachment to the amide nitrogen atom of an asparagine residue (N-linked oligosaccharide) or the oxygen atom of serine or threonine residues (Q-linked oligosaccharide). An increase in agalactosyl glycoforms of the IgG molecules (GO) of all subclasses has been observed for patients with certain inflammatory diseases such as rheumatoid arthritis (RA), tuberculosis, and Crohn's disease. A change in glycosylation of IgG has also been observed in CF patients with a large proportion of structures lacking galactose and fucose, which means that IgG glycosylation profile in cystic fibrosis (CF) is similar to that in RA. The decrease in galactose content of IgG would cause a decrease in clearance rate and could be responsible for the raised levels of IgG and ICs seen in older CF patients.