TISSUE-SPECIFIC GALACTOSYLTRANSFERASE ABNORMALITIES IN AN EXPERIMENTAL-MODEL OF RHEUMATOID-ARTHRITIS

Objective. - To investigate whether the observed pathophysiological si milarities that develop in both the collagen induced experimental mode l of arthritis (CIA) and rheumatoid arthritis (RA) are associated with similar glycosylation changes, and to evaluate possible differences i n the relative activity of the glycosylation enzyme beta, 1-4 galactos yltransferase (GTase) within various tissues, and thus provide a new i nsight into the potential pathogenic mechanisms controlling glycosylat ion changes. Methods. - Lymphocytic membrane-bound GTase activity was examined in 30 mice with CIA, 30 age matched controls and 10 adjuvant treated non-arthritic DBA/1 mice. Tissue-specific changes were assesse d by comparison of GTase activity in peripheral (P,GTase) and paired s plenic lymphocytes, In addition, we also investigated the effect that these changes may exert on the overall extracellular level of this enz yme, by assaying serum GTase (S,GTase) activity in these and a further group of 27 arthritic and 20 control mice. To analyse this synthetic abnormality in greater depth and to investigate the relevance of these glycosylation changes to the pathogenesis of arthritis, we also exami ned the humoral regulatory component associated with this system by as saying for both anti-collagen as well as anti-GTase antibodies. Result s. - The induction of arthritis in DBA/1 mice results in a marked redu ction in P,GTase activity, compared with age-matched unimmunised mice and the adjuvant controls. In contrast to the P,GTase, splenic GTase a ctivity was found to be similar in all the groups examined. Correspond ingly, serum GTase activity was also found to be significantly lower i n the collagen induced arthritic mice. This overall reduction in beta, 1-4 GTase activity reflects the clinical severity of arthritis and is associated with increased levels of naturally occurring anti-GTase an tibodies. Conclusions. - The GTase defect seen in the peripheral B and T cells in rheumatoid arthritis is also evident in the arthritic DBA/ 1 mouse model of RA, This may indicate a common pathological process i n both rheumatoid disease and CIA, in which changes in glycosylation a re dependent on the aberrant modulation of GTase in circulating, but n ot splenic lymphocytes, The relative expression and activity of glycos yltransferases within various tissues may not only contribute to immun oglobulin G (IgG) glycosylation changes, but perhaps also the aberrant expression of cell surface carbohydrates and thus cell trafficking.