HLA MARKERS AND PREDICTION OF CLINICAL COURSE AND OUTCOME IN RHEUMATOID-ARTHRITIS

Objective, To evaluate HLA markers as early prognostic factors for dis ease severity in rheumatoid arthritis (RA). Methods. HLA genotyping wa s carried out in a retrospective analysis of 66 RA patients and in a p rospective study of 55 RA patients and 87 healthy controls using polym erase chain reaction-based methods for HLA-DRB1 specificities, DR4 all eles, and their linked DQB1 alleles, as well as HLA-B27. The clinical course of RA was assessed by clinical and radiologic scores, The impac t of HLA markers was evaluated by epidemiologic means in addition to m odeling rising multiple logistic regression analysis. Results. Shared epitope-positive (HVR3+) DR4 alleles and the HVR3 amino acid cassette QKRAA were associated with RA in both longstanding (relative risk [RR] 3.34 and 3.19) and recent-onset (RR 2.1 and 2.37) RA. In longstanding RA, radiologic evidence of severe joint destruction (Larsen score >1. 62) was seen more often in HVR3 shared epitope-positive patients than in epitope-negative patients (odds ratio [OR] = 25.67, chi(2) = 13.59, P = 0.0003), Moreover, rant. sum analysis of Larsen indices indicated significantly higher ranking for the presence of the RA-associated HV R3 cassettes (QKRAA, QRRAA) when expressed on a DR4 allele (P< 0.0001) , In the prospective study, DR 4-positive patients had a significantly increased risk (OR = 13.75, P = 0.00083) of developing bony erosions, In addition, HVR3 epitope-positive DR4-positive individuals had signi ficantly higher Larsen indices than did epitope-negative patients (P = 0.0083), In particular, the presence of the HVR3 epitope on DR4 resul ted in an increased a posteriori likelihood (0.91) of developing early erosive disease compared with an a priori risk of 0.62, Conversely, t he likelihood decreased to a minimum of 0.35 when the HVR3 epitope was absent. Conclusion. While the contribution of HLA typing to establish ing the diagnosis of RA is limited, HLA-DR genotyping and DR4 subtype determination provide valuable markers for the prognosis of joint dest ruction in RA.