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

• Published in: Arthritis and rheumatism 1998-10, Vol.41 (10), p.1772-1782
• Main Authors: Cannons, Jennifer Leigh, Karsh, Jacob, Birnboim, H. Chaim, Goldstein, Rose
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - pathology; Biological and medical sciences; Cell Adhesion; Cell Line; Cloning, Molecular; Diseases of the osteoarticular system; Female; Humans; Hypoxanthine Phosphoribosyltransferase - blood; Hypoxanthine Phosphoribosyltransferase - genetics; Inflammatory joint diseases; Male; Medical sciences; Middle Aged; Mutation; Osteoarthritis - blood; Synovial Membrane - cytology; T-Lymphocytes - enzymology; T-Lymphocytes - metabolism
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/1529-0131(199810)41:10<1772::AID-ART9>3.0.CO;2-C

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 β1 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.