Structural changes in the oligosaccharide moiety of human IgG with aging.
In order to elucidate the relationship between glycosylation of IgG and aging, oligosaccharide structures of human IgG purified from sera of men and women aged 18 to 73 years were investigated. Oligosaccharides were liberated quantitatively from IgG by hydrazinolysis followed by N-acetylation and were tagged with p-aminobenzoic acid ethyl ester. The oligosaccharide structures were then analyzed by HPLC in conjunction with sequential exoglycosidase digestion. All IgG samples were shown to contain a series of biantennary complex type oligosaccharides which consisted of +/-Galbeta1-4GlcNAcbeta1-2Manalpha1-6(+/-GlcNAcbeta 1-4)(+/-Galbeta1-4GlcNAcbeta1-2Man(alpha)1-3)Man(beta)1-+ ++4GlcNAcbeta1-4(+/- Fucalpha1-6)GlcNAc and their mono- and disialo glycoforms in different ratios. In female IgG samples only, the incidence of non-galactosylated oligosaccharides with non-reducing terminal GlcNAc residues increased with aging (r>0.8), whereas that of digalactosylated oligosaccharides decreased (r<-0.8). A weaker correlation was observed between aging and the incidence of neutral and monosialo oligosaccharides in female IgG (r=0.461 and r= -0.538, respectively) and between aging and the incidence of oligosaccharides with a bisecting GlcNAc in both male and female IgG samples (r=0.566 and r=0.440, respectively). In addition, a significant change with aging in the galactosylation of IgG oligosaccharides was observed in females in their thirties, fifties, and sixties (p<0.02, p<0.01, and p<0.04, respectively). These findings may contribute to our understanding of autoimmune diseases such as rheumatoid arthritis in which glycosylation is involved.
Shikata
K
K
Department of Applied Chemistry, Tokai University, Hiratsuka, Kanagawa, Japan.
Yasuda
T
T
Takeuchi
F
F
Konishi
T
T
Nakata
M
M
Mizuochi
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D011487:Protein Conformation
D007074:Immunoglobulin G; D009844:Oligosaccharides