Site-specific glycosylation of human immunoglobulin G is altered in four rheumatoid arthritis patients.
Alterations in the glycosylation of human IgG have been shown to occur in rheumatoid arthritis (RA). However, the precise nature and location of these changes have not been fully established. Therefore we carried out a detailed analysis of the oligosaccharides chemically released from intact human serum IgG and fragments of the molecule. Serum samples were from three healthy ('normal') individuals, and from four patients with RA. Site-specific glycolsylation of the glycoprotein was shown to occur, which extended to sites even within the Fab fragment. These were differences in galactosylation, sialylation and the presence of a bisecting N-acetylglucosomide. Disease related alterations were also shown to be site-specific. In particular, an increase in the proportion of agalactosylated oligosaccharides occurred on the Fc fragment in RA (P=0.057), but, in contrast to previous reports there was an increase on the light chain in the proportion of fully galactosylated, bisected and core fucosylated oligosaccharides (from 13% of total in normal to between 18 and 35% in RA, P=0.057)). There was also an Fab-specific increase in oligosaccharides bearing a bisecting N-acetylglucosamine and a core fucose (P=0.075) The site-specific glycosylation changes described in this paper reveal the complexity of the regulatory mechanism, perhaps reflecting the many levels at which regulation can occur.
Youings
A
A
Glycobiology Institute, Department of Biochemistry, University of Oxford, U.K.
Chang
S C
SC
Dwek
R A
RA
Scragg
I G
IG
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood*; D001665:Binding Sites; D015153:Blotting, Western; D002240:Carbohydrate Sequence; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006031:Glycosylation; D006801:Humans; D007128:Immunoglobulin Fragments / Q000032:analysis; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000032:analysis
D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D009844:Oligosaccharides