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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 created 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). Citrulline is most commonly formed as part of the ageing process of cells and cell proteins.

How is it used?

Rheumatoid arthritis (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 minimise 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.

CCP can be useful in diagnosing early RA. An elevated CCP can be found in a significant number of patients who have a negative RF, the classic test for RA, and therefore can help to make a diagnosis. According to the American College of Rheumatology, 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, minimising the associated complications and tissue damage.

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 criteria of RA). The reason it is useful in confounding clinical presentations is that CCP is a more specific test for RA then the traditional RF. According to American College of Rheumatology, approximately 95% of patients with a positive CCP will develop RA in the future.

When is it requested?

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 rheumatoid arthritis.

Both CCP and RF may be present in chronic viral infections (hepatitis C) and is some bacterial infections (Q fever).

What does the result mean?

As a rule, test results outside the context of clinical symptoms and signs cannot be judged. Nonetheless, if a patient is positive for both CCP and rheumatoid factor, it is very likely that they have rheumatoid arthritis and it is likely that they may develop a more severe form of the disease. If a patient is 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.

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

Is there anything else I should know?

The CCP test has been rapidly accepted as an important assessment tool, combined with RF, in early arthritis. Levels of the antibody have not been correlated with severity or complications of the rheumatoid arthritis.

Common questions

  • Should everyone be tested for CCP?

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

Last Updated: Thursday, 1st June 2023

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