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

Abstract

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 maximum 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 lymphocytes. 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 structures 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 agedependent variations in the expression of oligosaccharides in addition to those related to differences in cell type (6). Volume 167 May 1988 1731-1736 Materials and Methods Brief Definitive ReportSerum was obtained from 151 individuals of both sexes and varying in age from 1-70 yr . None of the individuals >15 yr old were known to have any pathological abnormalities, nor to have had any history of autoimmune disease, although some of the older individuals may have had subclinical levels of age-related diseases (such as osteoarthritis), but none has as yet presented with major symptoms. All children under the age of 15 yr who were studied were undergoing ear, nose, and throat surgery, hernia repairs, or treat-R. B. Parekh, R. A. Dwek, and T. W. Rademacher are members of the Oxford Glycobiology Unit, which is supported by the Monsanto Co .

Endoglycosidase treatment abrogates IgG arthritogenicity: Importance of IgG glycosylation in arthritis

“…Interestingly, elevated levels of agalactosyl glycoforms were found in female RA patients, while decreased levels were correlated with disease remission during gestation followed by postpartum recurrence [50]. The glycoform distribution of serum IgG was shown to change with age [51,52]. It has been suggested that low galactosylation of IgG may have a critical role in the pathology of autoimmune disorders such as RA and SLE [53][54][55], but can also occur through aging [56].…”

Effects of temporary low-dose galactose supplements in children aged 5–12 y with classical galactosemia: a pilot study

“…Conversely, the relative incidence of digalactosylated structures (G2) changes inversely to G0 whereas monogalactosylated structures are constant in both sexes (23). A high G0/ G1 or G0/G2 ratio indicates a higher level of agalactosylated structures relative to mono-or diagalactosylated N-glycans.…”

“…We determined peak % areas of agalactosylated (G0), mono-(G1) and digalactosylated (G2) structures to provide a quantitative measurement of galactose incorporation into released undigested IgG N-glycans. We focused on the G0/ G2 ratio because digalactosylated (G2) structures were found to vary more than (G1) structures which remain more constant in healthy individuals (6,23). The technical replicate coefficients of variations for IgG N-glycans was below 10%.…”

Polymorphism and expression of the galactosyltransferase‐associated protein kinase gene in normal individuals and galactosylation‐defective rheumatoid arthritis patients

“…No difference was seen in the level of expression of the protein kinase gene in pooled E+ or pooled E-lymphocytes of normal individuals (Figure 6). Furthermore, the level of expression of this gene did not appear to be substantially different in pooled lymphocytes from RA patients, whether the RNA was obtained from patients with a glycosylation defect (i.e., percentage of oligosaccharide chains lacking galactose is >2 SD from the mean of normal control values [30]) or from patients with normally glycosylated IgG (i.e., percentage of oligosaccharide chains lacking galactose is <2 SD from the mean of normal control values). Slight differences in intensity between the samples hybridized with the GTA protein kinase gene probe were shown, by rehybridization with a pactin probe, to be largely due to variations in the amount of RNA bound to the nylon membranes.…”