HPRT? mutant T cells in the peripheral blood and synovial tissue of patients with rheumatoid arthritis

OBJECTIVE: To investigate the frequency and characteristics of hprt- mutant T lymphocytes in the peripheral blood and synovium of rheumatoid arthritis (RA) patients compared with controls, and to correlate these findings with disease parameters. METHODS: An hprt- T cell assay was performed on blood and synovial samples from 93 RA patients, 8 osteoarthritis (OA) patients, and 19 control subjects. T cell clones were studied by flow cytometry and evaluated for fibronectin adhesion. RESULTS: RA patients showed a 5-fold increase in the frequency of mutant T cells in the peripheral blood compared with that in control peripheral blood, and a further 10-fold increase in the mutant T cell frequency in synovial tissue. In OA patients, the synovium also had a significantly higher frequency of hprt- mutant T cells compared with the peripheral blood, but at a lower level than in the rheumatoid synovium. RA peripheral blood mutant T cell clones displayed elevated fibronectin adhesion and beta1 integrin expression, similar to that observed in the RA synovial T cell lines. CONCLUSION: The origin of the mutated T cells in the peripheral blood of these patients appears to be the inflamed synovium of RA, and to a lesser extent, of OA, where the cells are exposed to a mitogenic and genotoxic environment.