Association of (Q)R/KRAA positive HLA-DRB1 alleles with disease progression in early active and severe rheumatoid arthritis

Objective. We have shown that HLA-DRB1 alleles influence inflammatory activ ity in patients with early active and severe rheumatoid arthritis (RA). The refore, we analyzed the effect of HLA-DRB1 alleles on disease progression i n patients with early RA during a clinical followup period of 18 months. Methods. Disease progression was defined by the Larsen Score, the Ritchie I ndex (RI), and the Health Assessment Questionaire (HAQ) score. Results, Patients carrying arthritogenic HLA-DRB1 alleles on one or both ha plotypes are characterized by increased radiological joint destruction (Lar sen Score). Further, (Q)R/KRAA homozygous patients were characterized by wo rse overall disease course (higher RI and HAQ), However, analysis of change s in joint effects (Delta -RI) and personal disability (Delta -HAQ) did not reveal significant differences between patients with or without disease as sociated HLA-DRB1 alleles. Conclusion. The predisposing genetic pattern with disease associated HLA-DR B1 alleles did not profoundly influence the therapeutic outcome. Our data s upport the role of the HLA-DRB1 gene locus in disease modulation of RA. The genetic predisposition due to HLA-DRB1, however, may have only a limited i nfluence on the therapeutic outcome in clinically severe cases of RA.