Ann Rheum Dis 64:1199-1204 doi:10.1136/ard.2004.029389
  • Extended report

Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis

  1. M M J Nielen1,
  2. A R van der Horst2,
  3. D van Schaardenburg1,
  4. I E van der Horst-Bruinsma3,
  5. R J van de Stadt1,
  6. L Aarden4,
  7. B A C Dijkmans3,
  8. D Hamann2
  1. 1Jan van Breemen Institute, Amsterdam, Netherlands
  2. 2Sanquin Diagnostics at CLB, Amsterdam
  3. 3VU University Medical Centre, Amsterdam
  4. 4Sanquin Research at CLB and Laboratory of Experimental Immunology, Academic Medical Centre, Amsterdam
  1. Correspondence to:
    Dörte Hamann
    Sanquin Diagnostic Services at CLB, Dept. of Autoimmune Diseases, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands;
  • Accepted 2 January 2005
  • Published Online First 7 January 2005


Background: The anti-cyclic citrullinated peptide (CCP) test has a high sensitivity and specificity for rheumatoid arthritis, although CCP is not the physiological target of the autoantibodies. Citrullinated fibrin is abundant in inflamed synovium

Objective: To assess the diagnostic and prognostic value of antibodies against citrullinated fibrinogen (ACF), a soluble precursor of fibrin, in comparison with IgM-rheumatoid factor (IgM-RF) and the second generation anti-CCP test.

Methods: In 379 patients with early arthritis (258 rheumatoid and 121 undifferentiated), the sensitivity, specificity, and positive predictive value of ACF, anti-CCP, and IgM-RF for diagnosing rheumatoid arthritis were calculated. Multivariate logistic regression analysis was used to assess the diagnostic and prognostic value (radiographic progression after two years) of the tests.

Results: The sensitivities of the ACF, anti-CCP, and IgM-RF tests were 55.8%, 57.8%, and 44.6%, with specificities of 92.6%, 94.2%, and 96.7%, respectively. Approximately 30% of the IgM-RF negative patients were positive for ACF or anti-CCP or both. The ACF and anti-CCP test had a high agreement in early arthritis (κ = 0.84). Of all baseline characteristics, the ACF test and the anti-CCP test were the best predictors for diagnosing rheumatoid arthritis at one year (odds ratio (OR) = 10.3 and 10.6, respectively) and for radiographic progression after two years (OR = 12.1 and 14.8).

Conclusions: ACF is as sensitive as anti-CCP and more sensitive than IgM-RF in diagnosing rheumatoid arthritis in early arthritis. The ACF test is also a good predictor of radiographic progression, with a performance similar to the anti-CCP test. The ACF test and the anti-CCP test are especially valuable in IgM-RF negative arthritis.


  • Published Online first 7 January 2005