HLA class III region and susceptibility to rheumatoid arthritis

Objective: We examined the contribution of the HLA class III region in susceptibility to rheumatoid arthritis (Ra). Methods: Patients with RA, healthy subjects and homozygous typing cell (HTC) lines were typed for HLA class I (A, B, C), class II (DR, DQ) and class III (D6S273, Bat 2, and TNFa microsatellites, and HSP7O promoter region) alleles by molecular techniques. Results: Based on the distribution of microsatellites D6S273, Bat2 and TNFa, and HSP70 promoter region alleles in HTCs and homozygous unrelated individuals, a class III region haplotype, D6S273 138 - HSP70c - Bat2 138 - TNFa2 was identified. This haplotype showed a significant primary association with susceptibility to RA in DRB 1 QKRAA/QRRAA epitope-negative patients. Conclusion: Since the QKRAA/QRRAA epitope does not provide any risk for disease susceptibility in RA - susceptibility DRB1 epitope-negative patients, the present data suggest that the class III region haplotype D6S273 138 - HSP70c - Bat2 138 - TNFa2 provides an additional risk for the develop merit of RA. These results show that two regions in MHC, class II (DRB1) and class III (D6S273 138 - HSP70c- Bat 2 138 - TNFa2), contribute to susceptibility to RA and more completely define the risk for development of the disease. (C) Copyright Clinical and Experimental Rheumatology 2000.