Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis

Ann Intern Med. 2010 Apr 6;152(7):456-64; W155-66. doi: 10.7326/0003-4819-152-7-201004060-00010.


Background: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis.

Purpose: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease.

Data sources: 10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies.

Study selection: Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 x 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria).

Data extraction: One reviewer abstracted data on patient characteristics, ACPA details, and 2 x 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions.

Data synthesis: 151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case-control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone.

Limitations: Most studies used a diagnostic case-control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed.

Conclusion: Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood*
  • Female
  • Humans
  • Male
  • Peptides, Cyclic / immunology*
  • Sensitivity and Specificity


  • Autoantibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide