If a patient has joint inflammation and/or undiagnosed or undifferentiated inflammatory polyarthritis (symptoms which may suggest but do not yet meet the criteria of RA) and the doctor suspects RA
A blood sample taken from a vein in your arm
The cyclic citrullinated peptide antibody (CCP) test detects the presence of anti-citrulline antibodies in the blood. Citrulline is an unusual amino acid (protein building block), which is created when the amino acid arginine is altered. There is speculation that conversion of arginine to citrulline resulting in “citrullinated” proteins in the lining of joints, may be the target of anti-CCP antibodies in RA, which may contribute to inflammatory process in RA.
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 and early diagnosis and on beginning treatment before the development of significant joint damage. Rheumatoid factor (RF) has been the main autoantibody test used to help in the diagnosis of RA and distinguish it from other types of arthritis and other inflammatory processes. However, the RF test has poor specificity for RA; it can be negative in patients who have clinical signs of RA and positive in many different patients who do not, e.g. in patients with infections or in the elderly.
CCP antibodies have a slightly better sensitivity for RA but their main advantage is that they are much more specific for diagnosis of RA, meaning that if present they are more likely to indicate the presence of RA.
CCP can also be useful in helping to diagnose early RA. An elevated CCP concentration may be found in a significant number of patients who have a negative RF result, 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). Anti-CCP positive early RA patients may develop a more erosive disease than those without anti-CCP. 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 requested to help evaluate the likely development of RA in patients with an undifferentiated polyarthritis (those whose symptoms might suggest but do not yet meet the full criteria of RA). The reason it is useful in difficult 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 can be requested along with an RF test when a patient has symptoms suggestive of RA, or has been diagnosed with an undifferentiated polyarthritis. In many cases, it may be used 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.
What does the test result mean?
Please remember that RA remains a clinical diagnosis and as a rule, test results on their own, outside the context of clinical symptoms and signs, cannot be interpreted. Nonetheless, if a patient is positive for both CCP and RF, it is very likely that they have RA and it is possible 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 important in determining whether a patient has RA versus some other inflammatory condition. Remember that RF, particularly weak RF results, can be found in patients with infections, and in the elderly.
If a patient is negative for both CCP and RF, then it is less likely that they have RA. It must be emphasised, once again however, that RA is a clinical diagnosis based on patient’s symptoms, examination, and radiology, and may be made in the absence of positive autoantibodies.
Is there anything else I should know?
Anti-CCP appears to be the strongest serological predictor for RA development among symptomatic at-risk patients. It is also worth noting that at present, there is simply no convincing evidence that repeated autoantibody assessments provide any useful clinical information about disease progression among these symptomatic at-risk patients.
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. CCP is best used in patients with suggestive features of RA, whose RF is negative. CCP is now also being used in specialist early arthritis clinics to identify patients with RA early.