ASSOCIATIONS OF HLA-DRB AND HLA-DQB GENES WITH 2 AND 5-YEAR OUTCOME IN RHEUMATOID-ARTHRITIS

Objective-To evaluate the clinical usefulness of genomic HLA typing du ring the first five years of established rheumatoid arthritis (RA). Me thods-The HLA-DRB and -DQB alleles were determined by restriction leng th polymorphisms and polymerase chain reaction amplification with sequ ence specific primers in 99 Swedish patients with RA. Clinical feature s after two and five years disease duration were related to the geneti c pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patien ts were in remission after five years. Disability was assessed by heal th assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. Results -Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB104 on one allele, and 26% had DRB1*04 on both alleles (all fr equencies significantly greater than in controls). Frequencies of DRB1 04 associated DQB*0301 and ''0302 were normal. Patients carrying DRB1 04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disabilit y did not vary with regard to the genotype. Homozygous HVR3 patients h ad about three times greater risk of undergoing joint replacement; Hom ozygosity for HVR3 and presence of DQB0302 both tended to be associat ed with erosive disease. Conclusions-We confirmed a strong association ofdisease with the presence of the shared epitope on one or two allel es. However, genotype was not strongly associated with disease severit y after two and five years disease duration, and thus the value of gen omic typing to select patients for early aggressive therapy is questio nable.