HLA CLASS-II AND T-CELL RECEPTOR-BETA CHAIN POLYMORPHISMS IN BELGIAN PATIENTS WITH RHEUMATOID-ARTHRITIS - NO EVIDENCE FOR DISEASE ASSOCIATION WITH THE TCRBC2, TCRBV8 AND TCRBV11 POLYMORPHISMS

Objectives-To investigate whether T-cell receptor (TCR) beta chain ger mline alleles, either alone or in combination with a particular HLA-ge notype, are associated with rheumatoid arthritis (RA). Methods-Three r estriction fragment length polymorphisms (RFLPs), detected with TCR co nstant (TCRBC2) and variable (TCRBV8, TCRBV11) gene segments were anal ysed in a representative group of Belgian, HLA class II-typed patients with RA, and in a group of Belgian control subjects. Results-The stud y confirmed the known association of RA with the HLA-DRB10401/0404 ge notype (RR = 2.14, 95% CI = 1.16-4.00) in the Belgian RA population. T his association was even more pronounced in the patients with more sev ere RA (RR = 3.26, 95% CI = 1.55-6.89). These data suggest that the HL A-DRB104 genotype can be used as a marker for disease severity. Simil ar frequencies in patients and controls were observed for all TCRB RFL Ps studied, and this was in spite of subgrouping the RA population acc ording to criteria for disease stratification. Conclusion-While a clea r association with HLA DRB10401/0404 is observed, no interactive effe cts were seen with RA, DR4, TCRBC2 and TCRBV alleles, implying that th e combined presence of these polymorphic markers does not cause an inc reased susceptibility to RA, and does not predispose for more aggressi ve RA, nor for familial aggregation of the disease. These results argu e against the hypothesis that TCRB polymorphisms play a crucial role i n the susceptibility for RA.