Ab1804

HLA class III region and susceptibility to rheumatoid arthritis

D.P. Singal, J. Li, Y. Zhu

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
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.

Key words
Bat2, D6S273, HSP70, TNFa, RA.

This study was supported by the Arthritis Society, Canada.

Please address correspondence and reprint requests to: Dr. D.P. Singal, Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, Canada L8N 3Z5.
E-mail: singald@fhs.csu.mcmaster.ca