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Immunogenetic Aspects of Disease Progression in Rheumatoid Arthritis

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In an ongoing collaborative prospective study aimed at the identification of prognostic factors for the development of erosive disease and clinical severity of disease in early rheumatoid arthritis (RA) [1], 48 patients were followed for more than 4 years, and 87 patients were seen for 2 years. Significant associations with progressive joint destruction, measured by the Larsen index, were observed after 2 and 4 years for three parameters: 1) the presence of rheumatoid factor IgM; 2) bony erosions present at study entry, and 3) HLA DRB1 markers. Patients who expressed the shared epitope on a DR4 allele had significantly higher Larsen indices after 2 years (0.86 vs 0.12; P = 0.0015) and after 4 years (1.22 vs 0.53; P = 0.002) of disease duration. Similarly, the presence of the epitope sequence on either DR1 or DR4 also resulted in higher Larsen indices for epitope-positive patients (0.59 vs 0.06; P = 0.006 after 2 years, and 1.0 vs 0.69; P = 0.03 after 4 years). A more severe radiologic outcome after 2 years (Larsen index > 0.7) was detected with a sensitivity of 0.7, 0.61, and 0.58 and a specificity of 0.42, 0.84 and 0.75 using RF IgM, erosiveness at initial presentation, and presence of the shared epitope on a DR4 as prognostic parameters. Most useful, however, was the combination of DR4 positivity and erosiveness at study entry as prognostic indicators of a more severe course of joint destruction (sensitivity 0.68; specificity 0.77).

In summary, seropositivity, early erosiveness, and RA-associated HLA-DRB1 markers are useful prognostic indicators of the progression of joint destruction. Moreover, this influence is sustained during the first four years of the course of the disease.


  1. Wagner U, Kaltenhauser S, Sauer H, et al: HLA markers and prediction of clinical course and outcome in rheumatoid arthritis. Arthritis Rheum. 1997, 40: 341-351.

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Wassmuth, R., Kaltenhäuser, S., Wagner, U. et al. Immunogenetic Aspects of Disease Progression in Rheumatoid Arthritis. Arthritis Res Ther 1 (Suppl 1), S02 (1999).

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