Increased production of circulating soluble co-stimulatory molecules CTLA-4, CD28 and CD80 in patients with rheumatoid arthritis.

Co-stimulatory molecules are key immunoregulatory mediators in regulating T lymphocyte-mediated immune responses and inflammatory reactions. Here we investigated whether there is altered expression and the clinical significance of circulating soluble co-stimulatory molecules in rheumatoid arthritis (RA) patients. Serum concentrations of sCTLA-4, sCD28, sCD80 and sCD86 in 56 RA patients, and 32 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay (ELISA). Results showed that serum sCTLA-4, sCD28, and CD80 but not CD86 concentrations in all RA patients were significantly higher than concentrations in healthy control subjects. And there was significant and positive correlation between serum CTLA-4 and sCD28, sCD28 and sCD80, or sCTLA-4 and sCD80 in all RA patients. Serum sCTLA-4 concentration in all RA patients correlated significantly with disease activity score in 28 joints (DAS28). Moreover, immunosuppressant treatment with leflunomide could downregulate the increased levels of sCTLA-4, sCD28, and CD80 in RA patients. Therefore, the elevated production of circulating soluble T-cell co-stimulatory molecules should contribute to the pathogenesis of RA, and serum sCTLA-4 could potentially serve as a new marker of RA disease activity.