CCP: Ask Us | Cyclic Citrullinated Peptide Antibody

At a Glance

Why Get Tested?

To help diagnose rheumatoid arthritis (RA) and differentiate it from other types of arthritis; sometimes to help evaluate the prognosis of a patient with RA

When to Get Tested?

When a doctor suspects RA in a patient who has joint inflammation and/or undiagnosed or undifferentiated inflammatory arthritis, with symptoms that suggest but do not yet meet the criteria of RA

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

The Test Sample

What is being tested?

The cyclic citrullinated peptide antibody (CCP) test is a relatively new assay that detects the presence of citrulline antibodies in the blood. These autoantibodies are proteins produced by the immune system in response to a perceived threat from citrulline. An unusual amino acid, citrulline is produced when the amino acid arginine is altered. There is speculation that the conversion of arginine to citrulline may play a role in the autoimmune inflammatory process seen in the joints of those with Rheumatoid arthritis (RA).

RA is a chronic systemic autoimmune disease that causes inflammation, pain, stiffness, and destructive changes in the hands, feet, and other joints throughout the body. There are a variety of treatments available to minimize the complications of RA, but they depend on making an accurate diagnosis and on beginning treatment before the development of significant joint damage. Rheumatoid factor (RF) has been the primary blood test used to detect RA and distinguish it from other types of arthritis and other inflammatory processes. However, the sensitivity and specificity of RF are not ideal; it can be negative in patients who have clinical signs of RA and positive in patients who do not. Studies have shown that CCP has a sensitivity and specificity that is equal to or better than RF and is more likely to be positive with early RA.

According to the American College of Rheumatology (ACR), CCP antibodies may be detected in about 50-60% of patients with early RA, as early as 3-6 months after the beginning of symptoms. Early detection and diagnosis of RA allows doctors to begin aggressive treatment of the condition, minimizing the associated complications and tissue damage.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

The Test

How is it used?

A CCP test may be ordered along with or following a Rheumatoid factor (RF) test to help diagnose Rheumatoid arthritis (RA). CCP may also be ordered to help evaluate the likely development of RA in patients with undifferentiated arthritis – those whose symptoms suggest but do not yet meet the ACR criteria for RA. According to American College of Rheumatology, approximately 95% of patients with a positive CCP will develop RA in the future.

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When is it ordered?

CCP is primarily ordered along with an RF test when a patient has previously undiagnosed inflammatory arthritis or has been diagnosed with undifferentiated arthritis. It may be ordered as a follow-up test to a negative RF test when clinical signs, such as symmetrical joint pain and inflammation, lead the doctor to suspect RA.

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What does the test result mean?

As a rule, test results outside the context of clinical signs and symptoms cannot be judged. Nonetheless, when patients are positive for both CCP and RF, it is very likely that they have RA and it is likely that they may develop a more severe form of the disease. When patients are positive for CCP but not RF and clinical signs suggest RA, then it is likely that they have early RA or that they will develop RA in the future.

When patients are negative for CCP but have a positive RF, then the clinical signs and symptoms are more vital in determining whether they have RA or some other inflammatory condition. When patients are negative for both CCP and RF, then it is less likely that they have RA. It must be emphasized, however, that RA is a clinical diagnosis and may be made in the absence of positive autoantibodies.

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Is there anything else I should know?

The CCP test is promising and becoming more widely used; however, its ultimate clinical usefulness and the ways in which it will be used have yet to be fully determined.

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Common Questions

Should everyone be tested for CCP?

1. Should everyone be tested for CCP?

No. CCP is not recommended as a screening test. Like RF, it is best used for patients whose clinical signs suggest RA or who have already been diagnosed with undifferentiated arthritis.

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Related Pages

On This Site

Conditions: Rheumatoid arthritis, Autoimmune disorders

Elsewhere On The Web

American College of Rheumatology: Rheumatoid Arthritis
American College of Rheumatology: The Use of Anti-cyclic Citrullinated Peptide (anti-CCP) Antibodies in RA
Arthritis Foundation: Rheumatoid Arthritis

» See all Article Sources

Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 326.

Kelly, J. (2005 February 25). Anti-CCP plus RF may help find patients in the "treatment-window" stage of early RA. Medscape Medical News [On-line information]. Available online at http://www.medscape.com/viewarticle/538139 through http://www.medscape.com. Accessed on 8-26-08.

van der Helm-van Mil, A. et. al. (2005 June 30). Antibodies to Citrullinated Proteins and Differences in Clinical Progression of Rheumatoid Arthritis. Medscape from Arthritis Res Ther. 2005;7(5):R949-R958 [On-line information]. Available online at http://www.medscape.com/viewarticle/507248 through http://www.medscape.com. Accessed on 8-26-08.

Smith, H. (2006 May 24, Updated). Rheumatoid Arthritis. eMedicine [On-line information]. Available online at http://www.emedicine.com/med/TOPIC2024.HTM through http://www.emedicine.com. Accessed on 8-26-08.

Emery, P. et. al. (2008 May 12). Clinical Identification and Treatment of a Rapidly Progressing Disease State in Patients With Rheumatoid Arthritis. Medscape from Rheumatology. 2008;47(4):392-398 [On-line information]. Available online at http://www.medscape.com/viewarticle/573156 through http://www.medscape.com. Accessed on 8-26-08.

Fox, D. (2008 July 30). The ACR-EULAR Collaboration: An Expert Interview With David A. Fox, MD. Medscape Rheumatology [On-line information]. Available online at http://www.medscape.com/viewarticle/577523 through http://www.medscape.com. Accessed on 8-26-08.

Niemeier, L. (2008 March 3). The Role of Anti-CCP in the Laboratory Diagnosis of Rheumatoid Arthritis. CAP Newspath [On-line information]. Available online at http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=newspath%2F0803%2Fanti_ccp.html&_state=maximized&_pageLabel=cntvwr through http://www.cap.org. Accessed on 8-26-08.

(© 2003). The Use of Anti-cyclic Citrullinated Peptide (anti-CCP) Antibodies in RA. American College of Rheumatology [On-line information]. Available online at http://www.rheumatology.org/publications/hotline/1003anticcp.asp through http://www.rheumatology.org. Accessed on 8/26/08.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Shiel, W. (2004 September 17, Reviewed). Citrulline Antibody. MedicineNet.com [On-line information]. Available online at http://www.medicinenet.com/citrulline_antibody/article.htm through http://www.medicinenet.com.

Check, W. (2003 June). Assay takes arthritis out of the gray zone. College of American Pathologists, Feature Story [On-line journal]. Available online at http://www.cap.org/apps/docs/cap_today/feature_stories/rheumarthritis_assay.html through http://www.cap.org.

Bizzarola, N. et. al. (2001). Diagnostic Accuracy of the Anti-Citrulline Antibody Assay for Rheumatoid Arthritis. Clinical Chemistry. 2001; 47:1089-1093. [On-line information]. Available online at http://www.clinchem.org/cgi/content/full/47/6/1089 through http://www.clinchem.org.

(2004 February 4, Updated). Cyclic Citrullinated Peptide (CCP): A New Serum Marker for Rheumatoid Arthritis. Foundation for Blood Research, Fact Sheet [On-line information]. Available online at http://www.fbr.org/publications/factsheets/fs-ccp.html through http://www.fbr.org.

Wiik, A., et. al. (2003). The Use of Anti-cyclic Citrullinated Peptide (anti-CCP) Antibodies in RA. American College of Rheumatology, Hotline [On-line article]. Available online at http://www.rheumatology.org/publications/hotline/1003anticcp.asp through http://www.rheumatology.org.

McCoy, T. (2003 October 24). Simple Blood Test May Predict The Development Of Rheumatoid Arthritis In Patients With Joint Pain. American College of Rheumatology, Arthritis News [On-line press release]. Available online at http://www.rheumatology.org/press/2003/pr1.asp through http://www.rheumatology.org.

Bas, S. et. al. (2002). Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Rheumatology 2002; 41: 809-814. [On-line journal]. Available online at http://rheumatology.oupjournals.org/cgi/content/full/41/7/809 through http://rheumatology.oupjournals.org.

Vallbracht, I., et. al. (2004). Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Annals of the Rheumatic Diseases 2004;63:1079-1084. [On-line abstract]. Available online at http://ard.bmjjournals.com/cgi/content/abstract/63/9/1079 through http://ard.bmjjournals.com.

Castelar Pinheiro, G., et. al. (2003 August 5). Anti–Cyclic Citrullinated Peptide Antibodies in Advanced Rheumatoid Arthritis. Annals of Internal Medicine, Letter, Volume 139 Issue 3, Pages 234-235. [On-line journal]. Available online at http://www.annals.org/cgi/content/full/139/3/234-a through http://www.annals.org.

(©2004). 0055256: Cyclic Citrullinated Peptide Antibody, IgG. ARUP's User's Guide [On-line test information]. Available online at http://www.aruplab.com/guides/ug/tests/0055256.jsp through http://www.aruplab.com.

Rauscher, M. (2003 October 28, Updated). Antibodies may help predict rheumatoid arthritis. MedicineNet.com, Reuters Health [On-line information]. Available online at http://www.medicinenet.com/script/main/art.asp?articlekey=25015 through http://www.medicinenet.com.

Douglas, D. (2004 September 21). Antibodies Predict Course of Early Arthritis. MedlinePlus Health Information from Reuters [On-line news, not available after 10/21/2004]. Available online at http://www.nlm.nih.gov/medlineplus/news/fullstory_20221.html through http://www.nlm.nih.gov.

Schellekens, G., et. al., (1998 January). Citrulline is an Essential Constituent of Antigenic Determinants Recognized by Rheumatoid Arthritis-specific Autoantibodies. J. Clin. Invest. Volume 101, Number 1, January 1998, 273-281 [On-line journal]. Available online at http://www.jci.org/cgi/content/abstract/101/1/273 through http://www.jci.org.

Dina Dadabhoy, M.D., University of Michigan, Division of Rheumatology.