HLA-DR1, DR4, AND DRB1 DISEASE-RELATED SUBTYPES IN RHEUMATOID-ARTHRITIS - ASSOCIATION WITH SUSCEPTIBILITY BUT NOT SEVERITY IN A CITY WIDE COMMUNITY-BASED STUDY

Objective, To determine the relationship of DR1, DR4, and DR4 subtypes with disease severity in patients with rheumatoid arthritis (RA). Met hods. We studied a cohort of 103 Caucasian patients with an onset of d isease in 1985, and 6 to 7 years of disease at the time of the study. All rheumatologists in Edmonton participated in the city wide study wh ich included hospital and community based patients with mild and sever e disease. HLA status was determined using polymerase chain reaction a mplification and amplified fragment length polymorphism typing, Outcom e measures included joint counts, radiological scores, and physical fu nctional status. Results. Fifty-six patients (54%) were DR4 positive, (OR = 2.3, 95% CI 1.4-3.6, compared to controls). This association was only statistically significant for seropositive patients (OR = 2.8 in seropositive patients and OR = 1.5 in seronegative patients). A highe r risk was observed for DR1/DR4 heterozygotes (OR = 6.8 in seropositiv e patients and OR = 1.7 in seronegative patients). No significant diff erences were observed in disease activity, joint counts, radiological scores, or functional status among patients carrying 1, 2 or no diseas e related alleles, although the prevalence of rheumatoid factor (RF) s howed a linear association with allele dose (0, 1, or 2). Conclusion. DR4 and in particular DR1/DR4 heterozygosity were related to susceptib ility to RA only in seropositive patients. RF was a better predictor o f severity than disease related HLA subtypes. These findings suggest t hat the effect of these alleles on severity may be related to seroposi tivity, or that perhaps, seropositive and seronegative RA are genetica lly distinct entities. The results of our study suggest that in commun ity based settings, which include patients with milder disease, DR1 an d DR4 disease related alleles increase susceptibility for RA, but are not clinically useful as predictors of longer term outcome.