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 activity in patients with early active and severe rheumatoid arthritis (RA). Therefore, we analyzed the effect of HLA-DRB1 alleles on disease progression in patients with early RA during a clinical followup period of 18 months.

METHODS

Disease progression was defined by the Larsen Score, the Ritchie Index (RI), and the Health Assessment Questionnaire (HAQ) score.

RESULTS

Patients carrying arthritogenic HLA-DRB1 alleles on one or both haplotypes are characterized by increased radiological joint destruction (Larsen Score). Further, (Q)R/KRAA homozygous patients were characterized by worse overall disease course (higher RI and HAQ). However, analysis of changes in joint effects (delta-RI) and personal disability (delta-HAQ) did not reveal significant differences between patients with or without disease associated HLA-DRB1 alleles.

CONCLUSION

The predisposing genetic pattern with disease associated HLA-DRB1 alleles did not profoundly influence the therapeutic outcome. Our data support 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 influence on the therapeutic outcome in clinically severe cases of RA.