Independent association of rheumatoid factor and the HLA-DRB1 shared epitope with radiographic outcome in rheumatoid arthritis

Objective. Findings of a recent study suggested that HLA-DRB1 alleles encod ing the rheumatoid arthritis (RA) "shared epitope" (SE) were not predictive of erosive damage at 2 years in patients with early inflammatory arthritis who were rheumatoid factor (RF) positive, but were predictive in those who were RE negative. The present study was undertaken to determine whether RF status was also important in the association between the SE and radiograph ic outcome in patients with longstanding RA. Methods. The association between radiographic outcome, HLA-DRB1, and RF sta tus was examined in 299 RA patients with established disease (5-30 years). Radiographic outcome was measured by scoring radiographs of the hands and f eet using the standard radiographs of Larsen. HLA-DRB1 typing was performed using polymerase chain reaction methodology. Results were stratified by RF status and analyzed by multiple regression. Results. An association between radiographic severity and the SE was found in RF-, but not RF+, patients. RF- patients carrying an SE allele had highe r Larsen scores than RF- patients lacking the SE, although there was no ass ociation with SE dosage. The mean Larsen score was significantly higher in RF+ patients than in RF- patients, but there were no differences between RF + patients with 0, 1, or 2 SE alleles. Multiple regression analysis confirm ed independent associations of RF and SE positivity with radiographic outco me. No significant associations were found between RF and the SE, or RF and individual SE alleles. Conclusion. Our data indicate that RF and the SE are independently associat ed with radiographic outcome in RA. In RF+ patients with longstanding RA, t here is no apparent association between the presence of the SE and radiogra phic damage. However, in RF-patients, although radiographic outcome is gene rally less severe, there is an association between severity and presence of the SE.