Tissue-specific galactosyltransferase abnormalities in an experimental model of rheumatoid arthritis

To investigate whether the observed pathophysiological similarities that develop in both the collagen induced experimental model of arthritis (CIA) and rheumatoid arthritis (RA) are associated with similar glycosylation changes, and to evaluate possible differences in the relative activity of the glycosylation enzyme beta, 1-4 galactosyltransferase (GTase) within various tissues, and thus provide a new insight into the potential pathogenic mechanisms controlling glycosylation changes.

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 assessed by comparison of GTase activity in peripheral (P.GTase) and paired splenic lymphocytes. In addition, we also investigated the effect that these changes may exert on the overall extracellular level of this enzyme, 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 examined the humoral regulatory component associated with this system by assaying for both anti-collagen as well as anti-GTase antibodies.

The induction of arthritis in DBA/1 mice results in a marked reduction in P.GTase activity, compared with age-matched unimmunised mice and the adjuvant controls. In contrast to the P.GTase, splenic GTase activity was found to be similar in all the groups examined. Correspondingly, serum GTase activity was also found to be significantly lower in 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 antibodies.

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 in both rheumatoid disease and CIA, in which changes in glycosylation are dependent on the aberrant modulation of GTase in circulating, but not splenic lymphocytes. The relative expression and activity of glycosyltransferases within various tissues may not only contribute to immunoglobulin G (IgG) glycosylation changes, but perhaps also the aberrant expression of cell surface carbohydrates and thus cell trafficking.