Diagnostic performance of anti-citrullinated peptide antibodies for the diagnosis of rheumatoid arthritis: the relevance of likelihood ratios

Clin Chem Lab Med. 2010 Jun;48(6):829-34. doi: 10.1515/CCLM.2010.152.


Background: The goal of our study was to evaluate the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) assay in patients with autoimmune and inflammatory disorders.

Methods: We tested the specificity and sensitivity of anti-CCP2 antibodies measured by ELISA in 787 patients with rheumatoid arthritis (RA), 1024 patients with other autoimmune/inflammatory rheumatic disease and 401 subjects without autoimmune rheumatic disease. The optimal cut-off value was defined as the value with the highest diagnostic accuracy (receiver operating characteristic curve analysis). Interval-specific likelihood ratios (LRs) were calculated for each range bounded by defined anti-CCP2 values.

Results: To distinguish between patients with RA and controls, the cut-off value with the highest diagnostic accuracy for anti-CCP2 was 2.8 U/mL. Comparing the optimal cut-off value for anti-CCP2 to that recommended by the manufacturer (5.0 U/mL), an increase in prevalence between the proportions of test-positive patients was found for RA, undifferentiated connective tissue disease and undifferentiated arthritis. Evaluating interval-specific LRs for the selected ranges bound by two anti-CCP2 values, in RA and diseased controls, the LRs were 0.40 for values <5.0 U/mL, 6.66 for 5.0-15.0 U/mL, 27.01 for 15.1-30.0 U/mL and 28.89 for >30.0 U/mL.

Conclusions: The cut-off value of 2.8 U/mL for anti-CCP2 has the highest diagnostic accuracy. A value of anti-CCP2 >15 U/mL is associated with an increase in the likelihood of RA disease.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / diagnosis*
  • Autoantibodies / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Likelihood Functions
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • ROC Curve
  • Rheumatic Diseases / diagnosis


  • Autoantibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide