Prospective analysis of the impact of HLA-DR and -DQ on joint destruction in recent-onset rheumatoid arthritis

Objective. To evaluate the differential impact of HLA-DR and -DQ on the progression of erosive disease in the clinical course of early rheumatoid arthritis (RA). Methods. HLA genotyping for HLA-DR and -DQ was carried out in a prospective study of 87 patients with early RA. The progression of erosive disease was assessed by radiological scores over a period of 2 yr in all patients and over 4 yr in 77 patients. The impact of HLA markers was evaluated by univariate comparisons and by multiple logistic regression analyses. Results. Patients expressing the RA-associated shared epitope (SE) on a DRB1*01-positive or, most prominently, on a DRB1*04-positive allele had higher Larsen scores at all time-points analysed when compared with SE-negative patients. A similar impact on radiological progression was seen for the RA-predisposing DQ3, but not for DQ5 heterodimers. In the presence or absence of the DRB1 SE, no additional effects could be discerned for RA-associated DQ molecules. The presence of a DERAA-positive DRB1 allele was associated with a slower pace of joint destruction. While gene dosage effects were seen for SE compound homozygosity, no effect for DQ3 homozygosity could be discerned. Conclusion. Although a significant influence of HLA-DQ3 heterodimers on the progression of erosive joint destruction was seen, the analysis of the HLA-DQ locus did not add additional information over the study of HLA-DR including the determination of the SE and the DERAA motif in order to predict the development of severe progressive joint destruction.