Severe rheumatoid arthritis prohibits the pregnancy-induced decrease in alpha3-fucosylation of alpha1-acid glycoprotein.
Patients suffering from rheumatoid arthritis (RA) may experience a temporary reduction of disease symptoms during pregnancy. As indicated by the occurrence of RA-disease symptoms during pregnancy, three categories of patients were defined, namely, remission, relapse and unchanged. In all three categories changes in the plasma level and glycosylation of alpha1-acid glycoprotein (AGP) were determined longitudinally in comparison to those occurring in pregnancy of healthy women. In healthy pregnancy, we observed: (i) a peak in the plasma concentration at week 18 and a minimum at week 30; (ii) a continuous increase in the degree of branching of the glycans during the entire pregnancy period, and (iii) a decrease in the degree of alpha3-fucosylation of AGP-glycans with a minimum occurring at week 25. Comparable pregnancy-induced changes in glycosylation were found for two other acute-phase proteins alpha1-protease inhibitor (PI) and alpha1-antichymotrypsin (ACT). Increased oestrogen levels, known to occur during pregnancy, may be one of the factors that induce these changes, because the increased branching and decreased alpha3-fucosylation is in agreement with our earlier findings regarding an involvement of this hormone in the regulation of acute phase protein glycosylation in oestrogen-treated males as well as females. In all three clinical categories in RA, pregnancy also induced a continuous increase in the degree of branching of the glycans of AGP. However, similar changes in concentration and fucosylation were only found during remission of the disease symptoms. In the relapse and unchanged categories in RA, the degree of fucosylation and the plasma concentration of AGP remained constant throughout pregnancy. This indicates a relationship between changes in alpha3-fucosylation of AGP and RA disease activity.
Havenaar
E C
EC
Department of Medical Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Axford
J S
JS
Brinkman-van der Linden
E C
EC
Alavi
A
A
Van Ommen
E C
EC
van het Hof
B
B
Spector
T
T
Mackiewicz
A
A
Van Dijk
W
W
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005643:Fucose / Q000378:metabolism*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D009961:Orosomucoid / Q000737:chemistry / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry; D011247:Pregnancy / Q000378:metabolism*
D009961:Orosomucoid; D011134:Polysaccharides; D005643:Fucose