Anti-CCP Test for Rheumatoid Arthritis

This test detects autoantibodies which help confirm the diagnosis

Vials of blood for testing.
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The anti-CCP test is used to detect autoantibodies and help distinguish between rheumatoid arthritis and other inflammatory types of arthritis. The cyclic citrullinated peptide (CCP) antibody is an autoantibody against citrullinated proteins (ACPA) and is measured by this test.

The test has a relatively high sensitivity for rheumatoid arthritis, reportedly between 50 and 75 percent.

It also has an extremely high specificity for rheumatoid arthritis of about 90 percent. Its high specificity is why the anti-CCP test has become an important part of the diagnostic process for rheumatoid arthritis.

The Anti-CCP Test Diagnostic and Prognostic Value

Besides helping distinguish between inflammatory types of arthritis, the anti-CCP test is also extremely valuable in diagnosing people who are seronegative for rheumatoid factor. Not only does the anti-CCP test have diagnostic value (determining which condition you have), it also has prognostic value (predicting the course of your condition).

If anti-CCP is present at a moderate to high level, it not only helps to confirm the diagnosis, it suggests there may potentially be a more destructive and severe disease course, such as progressive joint damage. Low levels of the antibody are not as telling or predictive.

Usually, the anti-CCP test is ordered along with the rheumatoid factor test, since neither test alone can definitively confirm the diagnosis of rheumatoid arthritis.

According to rheumatologist Scott J. Zashin, "While rheumatoid factor is more common in people who have rheumatoid arthritis, there are people who are positive for rheumatoid factor who do not have rheumatoid arthritis. Furthermore, the presence of the rheumatoid factor has less prognostic significance than ACPA.

Also, if a person is negative for rheumatoid factor, they are less likely to be positive for ACPA."

Identifying Autoantibodies

The importance of identifying autoantibodies in rheumatic diseases had been recognized for decades, but identifying those that were clinically relevant in terms of specificity and sensitivity took time. There have been three generations of the anti-CCP test. With each generation of testing the specificity and sensitivity have improved.

According to "Kelley's Textbook of Rheumatology," more than 90 percent of people with undifferentiated arthritis who test positive for anti-CCP develop rheumatoid arthritis within three years. Only about 25 percent of those with undifferentiated arthritis who test negative for anti-CCP develop rheumatoid arthritis.

Autoantibodies may be detectable before the clinical onset of certain autoimmune diseases, including rheumatoid arthritis. Autoantibodies can precede the onset of seropositive rheumatoid arthritis by two to six years, according to "Kelley's Textbook of Rheumatology." Reportedly, measurable anti-CCP preceding the diagnosis of rheumatoid arthritis is twice as prevalent as detectable rheumatoid factor preceding the diagnosis.

While rheumatoid factor usually remains consistently present, the presence of anti-CCP can vary in rheumatoid arthritis patients—even disappearing in some cases.

The Significance of Anti-CCP

Researchers continue to look at what is happening in the body to produce molecules (antigens) that trigger the production of these anti-CCP antibodies. They are called autoantigens because they are produced by the breakdown of components within the body rather than coming from outside of the body. Peptidylarginine deiminase (PAD) enzymes, which catalyze the conversion of peptidylarginine to peptidylcitrulline, have a significant role in generating autoantigens in rheumatoid arthritis.

Also, more research is needed to determine what causes the pre-symptomatic phase of rheumatoid arthritis to shift into a symptomatic, full-fledged disease process.

While anti-CCP is highly specific for rheumatoid arthritis, positive results can occur with other autoimmune rheumatic diseases, tuberculosis, and chronic lung disease. Anti-CCP antibodies have been reported in systemic lupus erythematosus and primary Sjogren's syndrome, typically when erosive arthritis is present. It has also been found in up to 16 percent of people with psoriatic arthritis—most often with erosive or polyarthritis. Sometimes, it accompanies severe psoriasis without arthritis.

Sources:

Cush JJ, Kavanaugh A, Weinblatt ME. Rheumatoid Arthritis: Early Diagnosis and Treatment. West Islip, NY: Professional Communications; 2010.

Firestein GS, Kelley WN. Kelleys Textbook of Rheumatology. Philadelphia, PA: Elsevier/Saunders; 2013.

Taylor PC, Maini RN. Biologic Markers in the Diagnosis and Assessment of Rheumatoid Arthritis. UpToDate. https://www.uptodate.com/contents/biologic-markers-in-the-diagnosis-and-assessment-of-rheumatoid-arthritis.