Citrulline Antibody

  • Medical Author:
    Melissa Conrad Stöppler, MD

    Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

  • Medical Editor: William C. Shiel Jr., MD, FACP, FACR
    William C. Shiel Jr., MD, FACP, FACR

    William C. Shiel Jr., MD, FACP, FACR

    Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

What is citrulline antibody?

Citrulline antibody is an immune protein (antibody) that binds to a nonstandard amino acid (citrulline) that is formed by removing amino groups from the natural amino acid, arginine. A chemical process known as citrullination causes this change to occur. Citrulline antibodies are measured with a blood (serum) test that is analyzed in laboratories. The test is also known as anti-citrulline antibody, cyclic citrullinated peptide antibody (CCPA), anti-cyclic citrullinated peptide antibody, and anti-CCP.

Research suggests that in the joints of patients with rheumatoid arthritis, proteins may be changed to citrulline as part of the process that leads to inflammation of the rheumatoid joint.

For what is citrulline antibody used?

Citrulline antibody is present in the blood of most patients with rheumatoid arthritis. It is used in the diagnosis of rheumatoid arthritis when evaluating patients with unexplained joint inflammation. A test for citrulline antibodies is most helpful in looking for the cause of previously undiagnosed inflammatory arthritis when the substance detected by the traditional blood test for rheumatoid arthritis, rheumatoid factor, is not present. Citrulline antibodies have been felt to represent the earlier stages of rheumatoid arthritis in this setting and may be positive when the rheumatoid factor (RF) test is negative.

The citrulline antibody test then can be used by doctors to encourage them to proceed with the optimal treatments directed toward rheumatoid arthritis. Research has found that the presence of citrulline antibodies has also been associated with a greater tendency toward more destructive forms of rheumatoid arthritis.

Diagnosing Rheumatoid Arthritis

Citrulline Antibody Test

There is no singular test for diagnosing rheumatoid arthritis. The diagnosis is based on the clinical presentation. Ultimately, rheumatoid arthritis is diagnosed based on a combination of the presentation of the joints involved, characteristic joint swelling and stiffness in the morning, the presence of blood rheumatoid factor (RF test or RA test) and citrulline antibody, as well as findings of rheumatoid nodules and radiographic changes (X-ray testing). It is important to understand that there are many forms of joint disease that can mimic rheumatoid arthritis.

What is the normal range for the citrulline antibody test?

Normal results for the citrulline antibody test (negative result) are <20 EU/mL.

How are results of the citrulline antibody test reported?

Normal values (negative result) are <20 EU/mL. Positive results are classified as follows:

  • 20-39 EU/mL -- weakly positive
  • 40-59 EU/mL -- moderately positive
  • >60 EU/mL -- strongly positive

How specific is the citrulline antibody blood test for rheumatoid arthritis?

When the citrulline antibody is found in a patient's blood, there is a 90%-95% likelihood that the patient has rheumatoid arthritis. Citrulline antibody can also be positive in certain patients with other connective tissue disorders, such as systemic lupus erythematosus. It is also present in some healthy people.

What specialists order a citrulline antibody test?

The test is performed routinely in medical laboratories. Any physician can order the test to be done on a blood sample. Because the test is routinely performed for rheumatoid arthritis, pediatricians, internists, and rheumatologists are the physicians likely to order the test. The test is performed on a sample of venous blood collected by a routine blood draw.


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Kirksey, Duane. "Cyclic Citrullinated Peptide Antibody." Dec. 4, 2014. <>.