Shared rheumatoid epitope as a risk factor in determining outcome in rheumatoid arthritis

Background: A genetic component is thought to contribute to 30-40% of the expression of rheumatoid arthritis (RA) with the HLA-DR4, w4 (B1*0401), w14 (B1*0404) genes (and associated shared rheumatoid epitope) constituting a substantial portion of this risk. Aim: Our objective was to determine the presence of these risk factors in a group of patients with RA and to correlate presence with disease outcome. Method: Forty-three RA patients who had been regularly assessed up to a ten year period since their initial entry into two gold treatment trials were studied. DR4, w4:, w14 and shared rheumatoid epitope were determined on peripheral blood lymphocytes using flow cytometry and specific monoclonal antibodies. Disease outcome was measured by Health Assessment Questionnaire (HAQ) score and C-Reactive Protein (CRP) as a serological measure of joint inflammation. Results: To confirm accuracy of the now cytometric technique, DR typing and epitope status was compared with results obtained by genotyping in a subset of 14 patients. There was complete concordance between these two techniques for the rheumatoid epitope. However, concordance was not complete (both false positives and false negatives) for DR4, w4 and w14. Hence the presence of rheumatoid epitope was only evaluated further in the larger group. The presence of the shared rheumatoid epitope correlated positively with poorer outcome on serological assessment (p < 0.05). No significant correlation between HAQ score and rheumatoid epitope status was observed although a weak trend was noted. Conclusion: These studies suggest that determination of rheumatoid epitope status by now cytometry may provide useful data concerning the long term outcome of patients with RA.