A LINKAGE STUDY ACROSS THE T-CELL RECEPTOR-A AND T-CELL RECEPTOR-B LOCI IN FAMILIES WITH RHEUMATOID-ARTHRITIS

Objective. To examine whether the T cell receptor (TCR) A or TCRB loci exhibit linkage with disease in multiplex rheumatoid arthritis (RA) f amilies. Methods. A linkage study was performed in 184 RA families fro m the UK Arthritis and Rheumatism Council Repository, each containing at least 1 affected sibpair. The microsatellites D14S50, TCRA, and D14 S64 spanning the TCRA locus and D7S509, V beta 6.7, and D7S688 spannin g the TCRB locus were used as DNA markers. The subjects were genotyped using a semiautomated polymerase chain reaction-based method, Two-poi nt and multipoint linkage analyses mere performed. Results. Nonparamet ric single-marker likelihood odds (LOD) scores were 0.49 (P = 0.07) fo r D14S50, 0.65 (P = 0.04) for TCRA, 0.07 (P = 0.29) for D14S64, 0.01 ( P = 0.43) for D7S509, 0.0 (P = 0.50) for V beta 6.7, and 0.0 (P = 0.50 ) for D7S688, By multipoint analysis, there was no evidence of linkage at TCRB (LOD score 0), and the maximum LOD score at the TCRA locus wa s 0.37 (at D14S50). The presence of a susceptibility locus (LOD score < -2.0) was excluded, with lambda greater than or equal to 1.8 at TCRA and greater than or equal to 1.4 at TCRB. Conclusion. These linkage s tudies provide no significant evidence of a major germline-encoded TCR A or TCRB component of susceptibility to RA.