Glycosylation in health and disease

The glycome describes the complete repertoire of glycoconjugates composed of carbohydrate chains, or glycans, that are covalently linked to lipid or protein molecules. Glycoconjugates are formed through a process called glycosylation and can differ in their glycan sequences, the connections between them and their length. Glycoconjugate synthesis is a dynamic process that depends on the local milieu of enzymes, sugar precursors and organelle structures as well as the cell types involved and cellular signals. Studies of rare genetic disorders that affect glycosylation first highlighted the biological importance of the glycome, and technological advances have improved our understanding of its heterogeneity and complexity. Researchers can now routinely assess how the secreted and cell-surface glycomes reflect overall cellular status in health and disease. In fact, changes in glycosylation can modulate inflammatory responses, enable viral immune escape, promote cancer cell metastasis or regulate apoptosis; the composition of the glycome also affects kidney function in health and disease. New insights into the structure and function of the glycome can now be applied to therapy development and could improve our ability to fine-tune immunological responses and inflammation, optimize the performance of therapeutic antibodies and boost immune responses to cancer. These examples illustrate the potential of the emerging field of ‘glycomedicine’.Glycosylation refers to the addition of carbohydrate chains to proteins and lipids. In this Review, the authors discuss the broad role of glycans in immunity, cancer, xenotransplantation and glomerular filtration and the potential of ‘glycomedicine’.Key pointsGlycosylation is critical for physiological and pathological cellular functions; advances in analytical techniques have driven progression in the field of glycobiology over the past decade.Congenital disorders of glycosylation have provided considerable insight into basic mechanisms underlying the associations of specific glycoconjugates with disease phenotypes.Interactions between immune cells that are mediated by cell surface molecules and drive cellular activation are regulated by the glycosylation motifs of membrane-bound glycoconjugates and their binding to sugar-specific receptors.Cancers often exhibit oncofetal phenotypes that are reflected in the nature of their glycoconjugates; these changes in glycosylation drive metastatic properties, inhibition of apoptosis and resistance to chemotherapy.The pathogenesis of many autoimmune diseases, such as immunoglobulin A (IgA) nephropathy, systemic lupus erythematosus and inflammatory bowel disease, involves abnormal glycosylation of one or more glycoproteins; diabetes involves abnormal O-linked N-acetylglucosamine-mediated signalling and enhanced glycation of multiple proteins.Immunoglobulin glycosylation controls the effector functions of antibodies, which creates opportunities for the therapeutic application of glycoengineering.