Effects of low dose methotrexate therapy on the concentration and the glycosylation of alpha 1-acid glycoprotein in the serum of patients with rheumatoid arthritis: a longitudinal study.
OBJECTIVE
The concentration, and the degree of fucosylation and sialylation of human serum alpha 1-acid glycoprotein (AGP) were investigated for changes during 24-week low-dose methotrexate (MTX) or azathioprine treatment (AZA) in rheumatoid arthritis (RA) patients.


METHODS
Serum samples from a longitudinal study were analyzed by crossed affinoimmunoelectrophoresis with the fucose specific Aleuria aurantia lectin.


RESULTS
In general, the degree of fucosylation of AGP in RA sera was higher than in control sera, but decreased markedly under the influence of successful therapy with MTX. Concomitantly, the degree of sialylation of AGP increased and the concentration decreased. For alpha 1-protease inhibitor and haptoglobin similar results were obtained. In AZA responders less pronounced changes than in MTX responders were observed. In MTX nonresponders no significant trends were found. As in control sera, large interindividual differences in the AGP values were found.


CONCLUSIONS
The heavy fucosylation of AGP in RA sera reflects disease activity rather than an intrinsic characteristic of people genetically predisposed to RA, since it was found to decrease upon disease improvement. The differences in effects on AGP of MTX and AZA suggest either a gradual difference in a similar mechanism of action, or a different mechanism of action of the drugs. Fucosylated and sialylated AGP could be important in the etiopathogenesis of RA, because these molecules potentially can bind to adhesion receptors (selectins), which could prevent the extravasation of leukocytes into inflamed joints.
De Graaf
T W
TW
Department of Medical Chemistry, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Van Ommen
E C
EC
Van der Stelt
M E
ME
Kerstens
P J
PJ
Boerbooms
A M
AM
Van Dijk
W
W
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001379:Azathioprine / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006031:Glycosylation; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D006242:Haptoglobins; D009961:Orosomucoid; D000515:alpha 1-Antitrypsin; D001379:Azathioprine; D008727:Methotrexate