Rheumatology 2000; 39: 1189-1201
© 2000 British Society for Rheumatology
Skewed T-cell receptor variable gene usage in the synovium of early and chronic rheumatoid arthritis patients and persistence of clonally expanded T cells in a chronic patient
Biomedisch Onderzoeksinstituut DWI, Limburgs Universitair Centrum, Diepenbeek, Belgium
Objective. Autoreactive T cells may contribute to the pathogenesis of rheumatoid arthritis (RA). We studied the T-cell receptor (TCR) V-gene repertoire in the blood and synovium of early and chronic RA patients using polymerase chain reactionenzyme-linked immunosorbent assay to evaluate possible differences between these patient groups.
Results. Over-represented TCR V genes were observed in the synovium, but not in the blood of all RA patients (n = 38). The number of over-represented V genes was higher in the synovium of chronic RA patients (n = 31) than in that of early RA patients (n = 7). The V-gene profile was different among patients, and similar in the two knees for patients with bilateral synovitis (n = 5). The clonal composition of over-represented TCR BV genes in a patient with early RA and a patient with chronic RA was further studied by CDR3 region sequence analysis. A high level of clonal diversity was found in the joints and the blood of the early RA patient, suggesting a polyclonal T-cell expansion. In the chronic RA patient, predominant clonal expansions were observed in the blood and synovium, and some expanded clones were still present 2 yr later.
Conclusions. The observation of similar T-cell populations in both joints in patients with bilateral synovitis and the persistence of clonally expanded T cells for more than 2 yr in the joints of a chronic RA patient may indicate a pathogenic role for these cells in the disease process.
KEY WORDS: Rheumatoid arthritis, Autoimmunity, T-cell receptor usage, Clonal expansion, Synovial T cells.
Correspondence to: Dr P. Stinissen, Autoimmune Disease Unit, Biomedisch Onderzoeksinstituut DWI, Limburgs Universitair Centrum, Universitaire Campus, B-3590 Diepenbeek, Belgium.