Skip to content


Open Access

Immunogenetic Aspects of Disease Progression in Rheumatoid Arthritis

  • Ralf WassmuthMD1,
  • Sylke KaltenhäuserMD2,
  • Ulf WagnerMD2,
  • Sybille ArnoldMD2,
  • Wolfram SeidelMD2,
  • Michael TröltschMD2,
  • Ernst SchusterMD3,
  • Markus LöfflerPhD3,
  • Joachim R KaldenMD1 and
  • Holm HäntzschelMD2
Arthritis Research & Therapy19991(Suppl 1):S02

Published: 15 November 1999


Rheumatoid ArthritisPrognostic IndicatorStudy EntryJoint DestructionEarly Rheumatoid Arthritis

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


  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.PubMedView ArticleGoogle Scholar


© Current Science Ltd 2000