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

The clinical expression of rheumatoid arthritis (RA) varies considerablyamong individual patients. Genetic variations in human leucocyte antigen(HLA) may influence clinical expression. We re- examined the association ofHLA-DR with susceptibility to and clinical expression of RA using genomictissue typing, since most studies were based on (less reliable) serologicaltechniques. Seventy-eight patients with recent-onset RA, all participatingin a clinical trial on therapeutic strategies, were HLA-DR typed by meansof low-resolution genomic typing. Cumulative disease activity within thefirst 3 yr of disease was measured. Of the RA patients, 54% expressed DR4(DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patientshad a higher cumulative disease activity than RF-negative patients.Patients who were either DR1+ or DR4+ had a higher cumulative diseaseactivity than those who expressed neither DR1 nor DR4. This association wasless obvious after correction for RF status. The association of DR52+ (DR3,5, 6) and a lower cumulative disease activity could also not bedemonstrated 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 associatedwith the severity of RA. DR4 was associated with susceptibility to RA inour patients; HLA-DR low-resolution genomic tissue typing did not yieldadditional information to RF status for the clinical identification ofindividual patients with a poor prognosis.