engleski

Variability and heritability of immunoglobulin G glycosylation

Immunoglobulin G (IgG) is the most abundant glycoprotein in the human plasma and a major effector molecule of the humoral immune response. Glycans are essential structural components of the IgG antibody and even small changes in glycan composition can have a profound influence on IgG effector function by modulating binding to the Fc receptors. A development of the high-throughput IgG purification from plasma and optimization of chromatographic method for IgG glycan analysis of high resolution and sensitivity enabled a first large-scale study of IgG N-glycome in a population. Results from over 2000 individuals revealed a very high variability while heritability of IgG glycans was generally between 30 and 50%. Subclass-specific IgG Fc N- glycosylation analysis showed a significant age and sex-dependance. The most prominent changes in glycosylation in females were observed during menopausal age. Age-dependant changes in children differed from changes in adult population in both, direction and intensity. Genome-wide association study (GWAS) of the IgG N-glycome identified nine genetic loci that control IgG glycosylation.

IgG; N-glycans; HILIC; variability; heritability; aging; gender; IgG subclass specificity; GWAS

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