What Is the Anti-CCP Test for Rheumatoid Arthritis?

Detects Autoantibodies Which Help Confirm the Diagnosis

Vials of blood for testing.
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The CCP (cyclic citrullinated peptide) antibody is an autoantibody against citrullinated proteins (ACPA). The anti-CCP test is able to detect the autoantibodies against citrullinated proteins which have a relatively high sensitivity (reportedly between 50 and 75 percent) for rheumatoid arthritis and extremely high specificity (about 90 percent) for rheumatoid arthritis. 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: Its Diagnostic and Prognostic Value

The anti-CCP test helps to distinguish rheumatoid arthritis from other inflammatory types of arthritis. It is also extremely valuable in diagnosing people who are seronegative for rheumatoid factor. Not only does the anti-CCP test have diagnostic value, it also has prognostic value. 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 (i.e., 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, MD, "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 3 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 2 to 6 years, according to Kelley's Textbook of Rheumatology. Reportedly, anti-CCP that precedes the diagnosis of rheumatoid arthritis is twice as prevalent as rheumatoid factor that precedes 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

As researchers work to determine the cause (i.e., etiology and pathogenesis) of rheumatoid arthritis, defining which antigens promote the formation of autoantibodies against citrullinated proteins is an important task.

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 the specificity of anti-CCP is very high 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:

Autoantibodies in Rheumatoid Arthritis. Chapter 56. Elsevier. Ninth edition.

Cush, Weinblatt, and Kavanaugh. Rheumatoid Arthritis: Early Diagnosis and Treatment. CCP Antibodies. Page 68. Professional Communications, Inc. Third edition.

Taylor and Maini.Biologic Markers in the Diagnosis and Assessment of Rheumatoid Arthritis. UpToDate. Last Reviewed January 2017.

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