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
A. Vanderborght et al., 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, RHEUMATOLOG, 39(11), 2000, pp. 1189-1201
Objective. Autoreactive T cells may contribute to the pathogenesis of rheum
atoid arthritis (RA). We studied the T-cell receptor (TCR) V-gene repertoir
e in the blood and synovium of early and chronic RA patients using polymera
se chain reaction-enzyme-linked immunosorbent assay to evaluate possible di
fferences between these patient groups.
Results. Over-represented TCR V genes were observed in the synovium, but no
t 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 p
atients, and similar in the two knees for patients with bilateral synovitis
(n = 5). The clonal composition of over-represented TCR BV genes in a pati
ent 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 th
e joints and the blood of the early RA patient, suggesting a polyclonal T-c
ell expansion. In the chronic RA patient, predominant clonal expansions wer
e observed in the blood and synovium, and some expanded clones were still p
resent 2 yr later.
Conclusions. The observation of similar T-cell populations in both joints i
n patients with bilateral synovitis and the persistence of clonally expande
d T cells for more than 2 yr in the joints of a chronic RA patient may indi
cate a pathogenic role for these cells in the disease process.