Age-related galactosylation of N-linked oligosaccharides of human serum IgG

Immunological competence is known to vary with age, and such age-related variations are often parabolic in nature. For example, both the level and avidity of the antibody response increase during postnatal development, reach a maxi-mum in adulthood, and then decline during senescence (1). Cellular changes in the T lymphocyte compartment (both helper and suppressor T cell levels) appear to account for most variations in immunological competence (1, 2). Relatively few studies have attempted to correlate these functional changes with variations in the levels and nature of molecules expressed by immunocompetent lympho-cytes. A study has therefore been undertaken to evaluate the glycosylation status of IgG during the natural history of human life. Human serum IgG has been reported to carry at least 30 different N-linked oligosaccharides, all of which are of the biantennary complex type, and most of which (>95%) carry N-acetylglucosamine in both outer arms (3, 4). Structural differences between these arise primarily from core-substitutions (i.e., fucose and the `bisecting ' G1cNAc), outer-arm galactosylation, and sialylation (Fig. 1 a). We have previously reported that the percentage incidence of agalactosyl struc-tures on the serum IgG of a group of patients with active rheumatoid arthritis (mean age 62 yr) was-51%, placing this group well above the average for a group of normal individuals (3, 5). We now report that the galactosylation of IgG N-linked oligosaccharide changes as a parabolic function of age. This seemingly parallels changes in immunological competence and draws attention to the need to monitor age-dependent variations in the expression of oligosaccharides in addition to those related to differences in cell type (6)