engleski

Systems glycobiology: immunoglobulin G glycans as biomarkers and functional effectors in aging and diseases

Immunoglobulin G (IgG) is one of the key molecules of our immune system. With its Fab portion binding to the antigen and the Fc portion binding to various receptors and thus initiating a plethora of diverse downstream effector functions, IgG serves as a link between adaptive and innate immunity. Each of its heavy chains bears a diantennary N-glycan linked to the asparagine 297 within a conserved glycosylation site and the IgG3 subclass also carries O-glycans attached to its long hinge region. In addition, 15-20% IgG molecules bear N-glycans in the Fab portion, linked to the glycosylation sites that are newly acquired during somatic hypermutation. Both Fab and Fc glycans represent structurally and functionally relevant parts of the molecule, their composition modulating IgG stability, half-life, and effector functions. More than 30 different N- glycan compositions can be found at each of the IgG N-glycosylation sites, making any human serum a heterogeneous mixture of probably over a thousand different IgG glycovariants at any given time. The composition of IgG glycome is regulated by an intricate interplay of genetic and environmental factors, resulting in its substantial inter-individual variability. Levels of particular structural groups of glycans are known to change in association with various physiological states, such as age, sex, pregnancy, and menopause ; as well as in association with diseased states, such as inflammatory diseases, autoimmune diseases, and cancer. This chapter will attempt to explain the biological relevance of IgG glycopattern variations and suggest how IgG glycosylation can be exploited in personalized medicine and the production of biopharmaceuticals.

aging ; biological age ; biomarker ; biopharmaceuticals ; bisection ; diseases ; fucosylation ; galactosylation ; glycan ; glycosylation ; immunoglobulin G ; sialylation

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