No support for HLA-DQ encoded susceptibility in rheumatoid arthritis

OBJECTIVE: To test predictions based on data from immunogenetic and peptide-binding studies of collagen-induced arthritis in mice, in which it has been suggested that susceptibility to rheumatoid arthritis (RA) might be determined by the interaction between susceptibility alleles at the HLA-DQ locus and protective alleles at the HLA-DRB1 locus (including susceptibility effects for HLA-DQ7 and DQ8). METHODS: Predictions based on these models were tested in 166 healthy controls and 167 patients with RA, all of whom were typed for HLA-DRB1 and HLA-DQ alleles. RESULTS: In this population, HLA-DQ7 did not encode an increased risk for RA. This lack of susceptibility effect of HLA-DQ7 could not be attributed to competing HLA-DQ susceptibility alleles, protective HLA-DRB1 alleles, or the absence of DQA1*0301. CONCLUSION: These observations do not support the DR/DQ hypothesis in its present form.