Serum galactosyltransferase isoform changes in rheumatoid arthritis.
OBJECTIVE
To investigate glycosylation changes associated with rheumatoid arthritis (RA) by determining whether there are beta1,4-galactosyltransferase (GTase) isoforms specific to or altered in the serum of patients with RA. Methods. Serum GTase isoform profiles were determined using isoelectric focusing (IEF) in patients with active RA (n = 9), disease controls (DC; n = 9), and healthy individuals (HI; n = 10).


RESULTS
There was a highly significant difference (p < 0.0001) between the IEF profiles. The RA IEF profile was significantly (p < 0.0001) different from that of the DC or the HI group. There was, however, no significant difference between the DC and HI profiles. Serum GTase samples from 8/9 RA, 9/9 DC, and 9/10 HI resolved into 2 distinct peaks of activity. The RA isoform profile was associated with an acidic shift. There were no significant differences in the pH value of the first peak; the second peak was found to be significantly more acidic in the RA group (mean pH 5.02) compared to the DC and HI group (mean pH 5.20; p < 0.05). The RA associated isoform constituted a significantly greater proportion of total enzymatic activity in the RA sera (16.1%) compared to DC and HI (13.5%; p < 0.05 and 12.6%; p < 0.01, respectively). RA and HI serum GTase desialylation resulted in an alkaline shift of the isoforms into similar pH bands: 5.25-5.50, 5.70-5.85, and 6.20-6.40. GTase was found to be on average 75% more active in its desialylated form than in its sialylated state.


CONCLUSIONS
RA is associated with a differential expression of GTase isoforms. This may be due to increased hypersialylation, which has the potential to adversely affect the catalytic activity of the enzyme, thus providing a possible mechanism for posttranslational regulation of GTase activity in RA.
Alavi
Azita
A
Sir Joseph Hotung Centre for Musculoskeletal Diseases, St. George's Hospital and Medical School, London, United Kingdom. aalavi@sghms.ac.uk
Axford
John S
JS
Pool
Andrew J
AJ
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000201:enzymology*; D016022:Case-Control Studies; D002417:Cattle; D005260:Female; D005700:Galactosyltransferases / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000494:pharmacology
D007527:Isoenzymes; D005700:Galactosyltransferases; C493310:beta1,4-galactosyltransferase, human; D009439:Neuraminidase