Investigation into the concanavalin A reactivity, fucosylation and oligosaccharide microheterogeneity of alpha 1-acid glycoprotein expressed in the sera of patients with rheumatoid arthritis.
alpha 1-Acid glycoprotein (AGP) exists as an heterogeneous population of glycosylated variants (glycoforms) in plasma. The concentration of AGP increases some 2-5 fold in certain pathophysiological states exemplified by the chronic inflammatory disease, rheumatoid arthritis (RA). Moreover, the expressed glycosylation pattern alters in such conditions, indicating functional significance that is likely to be related to the oligosaccharide heterogeneity. We have investigated the heterogeneity of AGP glycosylation using the technique of high pH anion-exchange chromatography (HPAEC). AGP was isolated from the blood of RA sufferers, partially separated by Concanavalin A (Con A) affinity chromatography into bound and non-bound fractions and was enzymatically deglycosylated. Chromatography on the pellicular HPAE resin at pH 13 separated the released oligosaccharides and allowed a comparison of profiles in terms of branching and fucosylation. Results demonstrate an abnormal RA AGP glycosylation, with a tendency towards tri- and tetra-antennary oligosaccharides and enhanced fucosylation, in addition to the possible existence of penta-sialylated RA AGP glycoforms.
Elliott
M A
MA
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK.
Elliott
H G
HG
Gallagher
K
K
McGuire
J
J
Field
M
M
Smith
K D
KD
D001172:Arthritis, Rheumatoid / Q000097:blood*; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D003208:Concanavalin A; D006801:Humans; D009005:Monosaccharides / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D009844:Oligosaccharides / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D009961:Orosomucoid / Q000737:chemistry* / Q000302:isolation & purification; D013582:Synovial Fluid / Q000737:chemistry
D009005:Monosaccharides; D009844:Oligosaccharides; D009961:Orosomucoid; D003208:Concanavalin A