Immunogenetic Aspects of Disease Progression in Rheumatoid Arthritis

  • Ralf Wassmuth1,

    Affiliated with

    • Sylke Kaltenhäuser2,

      Affiliated with

      • Ulf Wagner2,

        Affiliated with

        • Sybille Arnold2,

          Affiliated with

          • Wolfram Seidel2,

            Affiliated with

            • Michael Tröltsch2,

              Affiliated with

              • Ernst Schuster3,

                Affiliated with

                • Markus Löffler3,

                  Affiliated with

                  • Joachim R Kalden1 and

                    Affiliated with

                    • Holm Häntzschel2

                      Affiliated with

                      Arthritis Res19991(Suppl 1):S02

                      DOI: 10.1186/ar16

                      Published: 15 November 1999

                      Full text

                      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.

                      Authors’ Affiliations

                      University of Erlangen-Nürnberg
                      University of Leipzig
                      Statistics and Epidemiology, Institute for Medical Informatics, University of Leipzig


                      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.View ArticlePubMed


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