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

Ann Rheum Dis. 2005 Aug;64(8):1199-204. doi: 10.1136/ard.2004.029389. Epub 2005 Jan 7.

Abstract

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 (kappa = 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.

MeSH terms

  • Adult
  • Aged
  • Arthritis / diagnosis*
  • Arthritis / immunology
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Citrulline / immunology*
  • Epidemiologic Methods
  • Female
  • Fibrinogen / immunology*
  • Humans
  • Immunoglobulin M / blood
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Prognosis
  • Rheumatoid Factor / blood
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Biomarkers
  • Immunoglobulin M
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Citrulline
  • Fibrinogen
  • Rheumatoid Factor