GENETIC TYPING OF PATIENTS WITH INFLAMMATORY ARTHRITIS AT PRESENTATION CAN BE USED TO PREDICT OUTCOME

Objective. To test the hypothesis that genetic characterization of pat ients at the time they present with inflammatory arthritis can predict subsequent destructive disease. Methods. We evaluated 177 patients wi th early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA ). Homozygosity in the patient's genotype was confirmed using restrict ion fragment length polymorphism analysis. The main outcome measure wa s radiologic erosions at 1 year. Results. At presentation, 120 patient s fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA popula tion, the frequency of Dw4/Dw14 compound heterozygotes was disproporti onately increased. The presence of either HVR3 or RF had a relative ri sk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/D w14 genotype developed erosions within 1 year. Conclusion. Knowledge o f a patient's HLA-DR type and RF status allows clinically useful predi ction of erosive disease; patients possessing Dw4/Dw14 represent a par ticularly high-risk subgroup.