Test Catalog

Test ID: CCP    
Cyclic Citrullinated Peptide Antibodies, IgG, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluating patients suspected of having rheumatoid arthritis (RA)


Differentiating RA from other inflammatory arthritis or connective tissue diseases

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by interactions between the environment, specific genetic risk factors, and the human immune system. It affects about 0.6% of the US population with a global prevalence of 0.24%.(1) Clinically, RA is typified by progressive damage of synovial joints, inflammation, production of diverse autoantibodies, and variable extra-articular manifestations.(2-4) Patients with RA may be categorized based on the phase of disease (early versus established), presence or absence of antibodies (seropositive versus seronegative), clinical manifestations (joint erosion, interstitial lung disease, or cardiovascular), or specific risks (genes, gender, or smoking).(2-4) Delayed diagnosis of RA is associated with joint erosion, destruction or deformities, poor response to treatment with ultimate increase in morbidity, and mortality.(3,4)


Although late RA prognosis may be linked to adverse consequences, early diagnosis has been reported to improve outcomes; notably reduced joint destruction or deformity, delayed radiologic progression, and decreased functional disability.(3-5) To facilitate early diagnosis, the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria recommend testing for rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA).(2) RF is an autoantibody directed against the Fc portion of immunoglobulin while ACPA are directed against peptides and proteins containing citrulline, a modified form of the amino acid arginine.(6,7) In addition to the use of RA and ACPA IgG to diagnose RA, RF and ACPA isotype antibodies and other serologic biomarkers have been used to predict if, and when, an individual who has inflammatory arthritis (IA) may develop future clinically apparent IA and access genetic and/or environmental risks.(3,4,8,9)


Compared to early serologic tests for RA including RF, several studies have demonstrated that ACPA have much improved specificity for RA.(4,6,10) A systemic review and meta-analysis of 33 studies including patients with RA and healthy or disease controls demonstrated the sensitivity of anti-mutated citrullinated vimentin, anticyclic citrullinated peptide, and RF of 71%, 71%, 77%, with the specificity of 89%, 95%, 73%, and the area under the curve of the summary receiver operating characteristic of 89%, 95%, 82%, respectively.(10) Based on these studies, there exist a subset of patients with RA who are negative for RF and ACPA IgG (seronegative) who must be diagnosed clinically or with use of emerging diagnostic tests.(4,7,9)


See Connective Tissue Disease Cascade (CTDC).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

<20.0 U (negative)

20.0-39.9 U (weak positive)

40.0-59.9 U (positive)

> or =60.0 U (strong positive)

Reference values apply to all ages.

Interpretation Provides information to assist in interpretation of the test results

A positive result for cyclic citrullinated peptide (CCP) antibodies may be suggestive of rheumatoid arthritis (RA) if compatible clinical features of disease are present.


Significantly elevated levels of CCP antibodies may be useful to identify RA patients with erosive joint disease.


A Mayo Clinic prospective clinical evaluation of the CCP antibody test showed a diagnostic sensitivity for RA of 78% with fewer than 5% false positive results in healthy controls (see Cautions).

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Positive results for cyclic citrullinated peptide (CCP) antibodies may occur in some patients with systemic lupus erythematosus or other autoimmune, connective tissue diseases. In a Mayo Clinic study (see Interpretation), the false-positive rate in this subgroup was approximately 10%.


Antirheumatic therapy should not be initiated based solely on a positive test for CCP antibodies, and changes in treatment should not be based upon the levels of CCP antibodies.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Cross M, Smith E, Hoy D, et al: The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014 Jul;73(7):1316-1322

2. Aletaha D, Neogi T, Silman AJ, et al: 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-2581

3. Burgers LE, Raza K, van der Helm-van Mil AH: Window of opportunity in rheumatoid arthritis - definitions and supporting evidence: from old to new perspectives. RMD Open. 2019 Apr 3;5(1):e000870

4. Deane KD, Holers VM: Rheumatoid arthritis pathogenesis, prediction, and prevention: An emerging paradigm shift. Arthritis Rheumatol. 2021 Feb;73(2):181-193

5. Emery P, Breedveld FC, Dougados M, Kalden JR, Schiff MH, Smolen JS: Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis. 2002 Apr;61(4):290-297

6. Schellekens GA, Visser H, de Jong BA, et al: The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000 Jan;43(1):155-163

7. Derksen VFAM, Huizinga TWJ, van der Woude D: The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin Immunopathol. 2017 Jun;39(4):437-446

8. Hedstrom AK, Ronnelid J, Klareskog L, Alfredsson L: Complex relationships of smoking, HLA-DRB1 genes, and serologic profiles in patients with early rheumatoid arthritis: Update from a Swedish population-based case-control study. Arthritis Rheumatol. 2019 Sep;71(9):1504-1511

9. Verheul MK, Bohringer S, van Delft MAM, et al: Triple positivity for anti-citrullinated protein autoantibodies, rheumatoid factor, and anti-carbamylated protein antibodies conferring high specificity for rheumatoid arthritis: Implications for very early identification of at-risk individuals. Arthritis Rheumatol. 2018 Nov;70(11):1721-1731

10. Zhu JN, Nie LY, Lu XY, Wu HX: Meta-analysis: compared with anti-CCP and rheumatoid factor, could anti-MCV be the next biomarker in the rheumatoid arthritis classification criteria? Clin Chem Lab Med. 2019 Oct 25;57(11):1668-1679

Special Instructions Library of PDFs including pertinent information and forms related to the test