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 HSP70 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 development 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.