HLA CLASS III REGION AND SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS.
DP Singal, J Li, Y Zhu, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

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We examined the distribution of HLA class III region in susceptibility to rheumatoid arthritis (RA). The 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 (D6S 273, Bat 2 and TNFa microsatellites, and HSP70 promoter region) alleles by molecular techniques. Based on the distribution of microsatellites D6S 273, Bat 2 and TNFa, and HSP70 promoter region alleles in HTCs and homozygous unrelated individuals, a class III region haplotype, D6S 273 138 - HSP70c - Bat 2 138 - TNFa 2, was identified. This haplotype showed a significant (p<0.0002, RR=12.1) positive association with susceptibility to RA in DRB1 QKRAA/QRRAA epitope- negative individuals. Since QKRAA/QRRAA epitope does not provide any risk for disease susceptibility in RA-susceptibility DRB1 epitope-negative patients, the present data suggest that class III region haplotype D6S 273 138 - HSP70c - Bat2 138 - TNFa2 provides an additional risk in the development of RA. The results suggest that two regions in MHC, class II (DRB1) and class III (D6S 273-HSP70-Bat2-TNFa), contribute to susceptibility to RA and more completely define the risk for development of disease.