ASSOCIATION OF RHEUMATOID-ARTHRITIS WITH AN AMINO-ACID ALLELIC VARIATION OF THE T-CELL RECEPTOR

Objective. To investigate allelic variations of T cell receptor residu es for a contribution to rheumatoid arthritis (RA) susceptibility. Met hods. We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive di sease and 813 control subjects. Productive changes of segments TCRAV6S 1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6SI, TCRBV6S7 were investig ated by single-strand conformation polymorphisms. The TCRAV8S1 associa tion was confirmed by restriction fragment length polymorphism. Result s. In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). Thi s finding was replicated in 2 further populations, one from France (21 2 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooli ng of the data and confirmation of the association (OR 1.3 [95% confid ence interval 1.1-1.7], P = 0.008). Conclusion. These findings show ev idence that TCRA is an RA susceptibility locus.