Immunoglobulin-Associated Glycans: Functions In Mucosal Defenses And Immunopathology

Glycans of immunoglobulins of all isotypes play an essential role in the immunoglobulin Fc-mediated effector functions. These include the half-life in the circulation, activation of the complement cascade by the lectin pathway, inhibition of adherence of bacteria to epithelial cells, and reactivity with receptors expressed on epithelial cells, NK cells, monocytes, and macrophages. Altered structures of glycan moieties of IgG have been reported in a number of human autoimmune and infectious diseases (e.g., rheumatoid arthritis, periodontitis, HIV and Mycobacterium tuberculosis infections). Deficient galactosylation of the hinge-region O-glycans of human IgA1 is involved in the most common glomerulonephritis, IgA nephropathy. As the result of disbalance of specific glycosyltransferases, some O-glycans became deficient in galactose. When the exposed terminal N-acetylgalactosamine residues become recognized by naturally occurring antibodies, immune complexes are formed in the circulation. Some of these large immune complexes with nephritogenic properties deposit in the glomerular mesangium and initiate the pathological changes. In the absence of causal therapy, approaches that prevent the formation of large complexes are currently explored. In summary, structural and functional studies of immunoglobulin-associated glycan deserve due appreciation as important participants in mucosal defence mechanisms, inhibitors of several immunologic processes, and, conversely, mediators of pathogenic processes.