What Is The Citrulline Antibody Test?

A newer blood test used to help diagnose RA is the citrulline antibody test, more formally known as the cyclic citrullinated peptide (CCP) antibody test. It may also be referred to as anti-citrulline antibody, anti-cyclic citrullinated peptide antibody (anti-CCP), or cyclic citrullinated peptide antibody IgG (CCP IgG).

Citrulline antibody

An antibody directed against an unusual amino acid called citrulline. Citrulline is not normally present in peptides or proteins in the body. The presence of high amounts of the citrulline antibody in the bloodstream suggests that the person is suffering from rheumatoid arthritis.

Like rheumatoid factor (RF), CCP is an antibody that is produced in a person who has an autoimmune disease. This antibody is directed against an unusual amino acid called citrulline. Citrulline is formed when amino groups are removed from arginine, a natural amino acid. Medical research suggests that in the joints of patients with RA, proteins may be changed to citrulline through some unknown process. The body's immune system treats this protein as foreign material and creates antibodies to it—that is, anti-CCP antibodies. These antibodies begin to attack the joints, in an action that some scientists believe causes the inflammation of the rheumatoid joint. Measuring the citrulline antibody provides the basis for a screening test for RA. Citrulline antibodies are measured with a blood test that is analyzed in a laboratory.

Compared with test for RF, the test for citrulline antibodies is both more sensitive and more specific for RA. A more sensitive test means that a higher percentage of people with RA will have a positive CCP test, as compared with the RF test. A more specific test means that when a person has a positive CCP result, he or she is more likely to truly have RA, as compared with having a positive RF test.

In one study, CCP antibodies were found in 76% of patients with confirmed RA, but a positive RF test was obtained in only 60% of the same patients. When patients had RA and tested positive for RF, the rate of positive CCP antibody tests increased to 90%. In patients with confirmed RA whose RF tests were negative, the CCP antibody test was positive in only 40%. In healthy volunteers, a CCP antibody test was positive in only 1% of patients—a better performance than the test for RF, which was positive in as many as 10% of healthy volunteers. Therefore, a positive CCP test is more likely to mean a true diagnosis of RA than a positive RF test. Further, the CCP test will give fewer false-positive results when compared to a RF test (1% versus 10%, respectively.)

The CCP antibody also appears earlier in the course of RA than RF, so the CCP test can be used to detect early-stage RA disease. In one study, this test was positive in patients with RA who had joint symptoms for only three to six months. Another study suggested that CCP antibodies may predate the onset of arthritis symptoms by several years in some patients. For all these reasons, it may be a good idea for people with positive CCP blood tests to visit their doctor on a regular basis, even if they have not been officially diagnosed with RA.