Association of HLA-DR with susceptibility to and clinical expression of rheumatoid arthritis: re-evaluation by means of genomic tissue typing

Br J Rheumatol. 1998 Apr;37(4):411-6. doi: 10.1093/rheumatology/37.4.411.


The clinical expression of rheumatoid arthritis (RA) varies considerably among individual patients. Genetic variations in human leucocyte antigen (HLA) may influence clinical expression. We re-examined the association of HLA-DR with susceptibility to and clinical expression of RA using genomic tissue typing, since most studies were based on (less reliable) serological techniques. Seventy-eight patients with recent-onset RA, all participating in a clinical trial on therapeutic strategies, were HLA-DR typed by means of low-resolution genomic typing. Cumulative disease activity within the first 3 yr of disease was measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patients had a higher cumulative disease activity than RF-negative patients. Patients who were either DR1+ or DR4+ had a higher cumulative disease activity than those who expressed neither DR1 nor DR4. This association was less obvious after correction for RF status. The association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could also not be demonstrated after correction for RF status. Among RF-negative patients, DR51+ (or DR2+) was associated with a higher cumulative disease activity. Other HLA-DR types (including DR1 and DR4 separately) were not associated with the severity of RA. DR4 was associated with susceptibility to RA in our patients; HLA-DR low-resolution genomic tissue typing did not yield additional information to RF status for the clinical identification of individual patients with a poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Female
  • Genome, Human
  • HLA-DR Antigens / genetics*
  • Histocompatibility Testing
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Rheumatoid Factor / blood


  • HLA-DR Antigens
  • Rheumatoid Factor