A T-CELL RECEPTOR BETA-CHAIN VARIABLE REGION POLYMORPHISM ASSOCIATED WITH RADIOGRAPHIC PROGRESSION IN RHEUMATOID-ARTHRITIS

Objective-In rheumatoid arthritis (RA) genetic factors influence susce ptibility to disease and progression. Identifying these genetic factor s may give more insight into the aetiology and pathogenesis of this di sease. Furthermore, if these genetic markers can predict progression i n an early stage of disease, timely institution of more aggressive tre atment in patients with a bad prognosis may help to prevent joint dama ge. Several studies have shown that HLA-DRB1 alleles are associated wi th RA, whereas others have indicated that genes not linked to the HLA complex are also involved. Candidates for such genes are the T cell re ceptor (TCR) alpha/beta genes. Methods-The association of a polymorphi sm in a TCR beta chain variable region gene (TCR-Vbeta8) with both ris k for RA and radiographic progression of joint disease was analysed af ter a three year follow up. A cohort of 118 white patients with a dura tion of disease shorter than one year at entry, and 110 white controls were typed for this (BamHI) TCR-Vbeta8 polymorphism. Results-The dist ribution of the two alleles, 2.0 and 23.0 kb, was identical in patient s and controls. Radiographic progression (modified Sharp method) after a three year follow up, studied in 111 patients, was significantly le ss in the group possessing the 2.0 kb allele (p=0.03). Conclusion-This does not confirm the reported association of the (BamHI) TCR-Vbeta8 2 .0 kb allele with RA. By contrast with previous findings in smaller st udies, in the present study this 2.0 kb allele was protective against radiographic progression. Because well known prognostic variables in R A were corrected for, the findings indicate that the TCR-Vbeta8 polymo rphism studied is a new prognostic marker for this disease.