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.


CONCLUSIONS
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.
Singal
D P
DP
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. singald@fhs.csu.mcmaster.ca
Li
J
J
Zhu
Y
Y
D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C092008:PRRC2A protein, human