Changes in normal glycosylation mechanisms in autoimmune rheumatic disease.
To investigate potential mechanisms controlling protein glycosylation we have studied the interrelationship between lymphocytic galactosyltransferase (GTase) activity and serum agalactosylated immunoglobulin G levels (G(0)) in healthy individuals and patients with rheumatoid arthritis and non-autoimmune arthritis. In RA there was reduced GTase activity and increased G(0). A positive linear correlation between B and T cell GTase was found in all individuals. The relationship between GTase and G(0) was found to be positive and linear in the control population and negative and linear in the RA population. Sulphasalazine therapy maintained normal levels of GTase and caused a reduction in G(0) in the RA population. IgG anti-GTase antibodies (abs) were significantly increased in the RA population, whereas IgM anti-GTase abs were significantly decreased in both the RA and the non-autoimmune arthritis groups. These data describe a defect in RA lymphocytic GTase, with associated abnormal G(0) changes, which is corrected by sulphasalazine. A possible regulatory mechanism controlling galactosylation in normal cells is suggested, in which there is parallel control of B and T cell GTase. IgM anti-GTase abs may be integrated into this normal regulatory process. This is disrupted in RA, where the positive feedback between GTase and G(0) is lost and there is an associated increase in IgG anti-GTase abs, which may result from isotype switching as IgM anti-GTase abs are reduced. We suggest that these mechanisms are of relevance to the pathogenesis of RA, and that their manipulation may form part of a novel therapeutic approach.
Department of Rheumatology Research/Immunology, University College and Middlesex School of Medicine, London, United Kingdom.
J S
JS
Axford
N
N
Sumar
A
A
Alavi
D A
DA
Isenberg
A
A
Young
K B
KB
Bodman
I M
IM
Roitt
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005700:Galactosyltransferases / Q000032:analysis*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D012460:Sulfasalazine / Q000494:pharmacology
D007074:Immunoglobulin G; C064155:agalactosyl IGG; D012460:Sulfasalazine; D005700:Galactosyltransferases