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Prediction models for rheumatoid arthritis during diagnostic investigation: evaluation of combinations of rheumatoid factor, anti-citrullinated protein/peptide antibodies and the human leucocyte antigen-shared epitope
  1. Bert Vander Cruyssen1,
  2. Ilse E A Hoffman1,
  3. Isabelle Peene1,
  4. Ann Union2,
  5. Herman Mielants1,
  6. Lydie Meheus2,
  7. Filip De Keyser1
  1. 1Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
  2. 2Innogenetics, Ghent, Belgium
  1. Correspondence to:
    Dr Bert Vander Cruyssen
    Department of Rheumatology, Ghent University Hospital, B-9000 Ghent, Belgium; bert.vandercruyssen{at}


Objectives: To calculate the probabilities for rheumatoid arthritis in a consecutive cohort of patients during diagnostic investigation. Different logistic regression models evaluating the value of human leucocyte antigen (HLA)-shared epitope determination and testing for rheumatoid factor and anti-citrullinated protein/peptide antibodies (ACPA) were fitted.

Methods: 1003 consecutive patients were included in the study, presenting a new diagnostic problem for which rheumatoid arthritis was included in the differential diagnosis. All patients were tested for ACPA, rheumatoid factor and HLA-shared epitope.

Results: After 1 year, diagnoses were established: 153 patients had definite rheumatoid arthritis and 629 patients had rheumatoid arthritis excluded. Rheumatoid factor, used as a continuous marker, is useful in evaluating the probability for rheumatoid arthritis. Combined rheumatoid factor and shared epitope testing may provide additional predictive information, but combined ACPA and rheumatoid factor testing is superior. The redundancy of shared epitope testing in a model that includes ACPA testing can be explained by the high association between ACPA and shared epitope both in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis. The value of rheumatoid factor testing increased if patients presented with at least one swollen joint at baseline.

Conclusion: Valid probabilities for rheumatoid arthritis during routine diagnostic investigation were calculated, and showed that the potential additional value of shared epitope testing disappears when ACPA testing is available. Combined rheumatoid factor and ACPA testing is useful, especially when rheumatoid factor is considered as a continuous parameter reflecting an increasing probability for rheumatoid arthritis at higher rheumatoid factor titres. The value of (continuous) rheumatoid factor testing increases when the a priori chance is higher.

  • ACPA, anti-citrullinated protein/peptide antibodies
  • HLA, human leucocyte antigen
  • LIA, line immunoassay
  • PepA, citrullinated peptide A
  • PepB, citrullinated peptide B
  • PPV, positive predictive value

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  • Published Online First 13 July 2006

  • Funding: BVC was supported by a concerted action grant GOA 2001/12051501 from Ghent University, Ghent, Belgium.

  • Competing interests: AU and LM are employees of Innogenetics, Ghent, Belgium.

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