Antibodies, Anti-Cyclic Citrullinated Peptide

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Antibodies, Anti-Cyclic Citrullinated Peptide

Synonym/acronym: Anti-CCP antibodies, ACPA.

Common use

To assist in diagnosing and monitoring rheumatoid arthritis.


Serum (1 mL) collected in a gold-, red-, or red/gray-top tube.

Normal findings

IgG Ab (Method: Immunoassay, enzyme-linked immunosorbent assay [ELISA])
NegativeLess than 20 units
Weak positive20–39 units
Moderate positive40–59 units
Strong positive60 units or greater


Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that damages the joints. Inflammation caused by autoimmune responses can affect other organs and body systems. The current American Academy of Rheumatology criteria focuses on earlier diagnosis of newly presenting patients who have at least one swollen joint unrelated to another condition. The current criteria includes four determinants: joint involvement (number and size of joints involved), serological test results (rheumatoid factor [RF] and/or ACPA), indications of acute inflammation (CRP and/or ESR), and duration of symptoms. A score of 6 or greater defines the presence of RA. Patients with long-standing RA, whose condition is inactive, or whose prior history would have satisfied the previous classification criteria by having four of seven findings—morning stiffness, arthritis of three or more joint areas, arthritis of hand joints, symmetric arthritis, rheumatoid nodules, abnormal amounts of rheumatoid factor, and radiographic changes—should remain classified as having RA. The study of RA is complex, and it is believed that multiple genes may be involved in the manifestation of RA. Scientific research has revealed an unusual peptide conversion from arginine to citrulline that results in formation of antibodies whose presence provides the basis for this test. Studies show that detection of antibodies formed against citrullinated peptides is specific and sensitive in detecting RA in both early and established disease. Anti-CCP assays have 96% specificity and 78% sensitivity for RA, compared to the traditional IgM RF marker with a specificity of 60% to 80% and sensitivity of 75% to 80% for RA. Anti-CCP antibodies are being used as a marker for erosive disease in RA, and the antibodies have been detected in healthy patients years before the onset of RA symptoms and diagnosed disease. Some studies have shown that as many as 40% of patients seronegative for RF are anti-CCP positive. The combined presence of RF and anti-CCP has a 99.5% specificity for RA. Women are two to three times more likely than men to develop RA. Although RA is most likely to affect people aged 35 to 50, it can affect all ages.

This procedure is contraindicated for



  • Assist in the diagnosis of RA in both symptomatic and asymptomatic individuals
  • Assist in the identification of erosive disease in RA
  • Assist in the diagnostic prediction of RA development in undifferentiated arthritis

Potential diagnosis

Increased in

  • RA (The immune system produces antibodies that attack the joint tissues. Inflammation of the synovium, membrane that lines the joint, begins a process called synovitis. If untreated, the synovitis can expand beyond the joint tissue to surrounding ligaments, tissues, nerves, and blood vessels.)

Decreased in


Critical findings


Interfering factors


Nursing Implications and Procedure


  • Patient Teaching: Inform the patient this test can assist in identifying the cause of joint inflammation.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • Obtain a history of the patient’s immune and musculoskeletal systems, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.


  • Potential complications: N/A
  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Perform a venipuncture.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis.


  • Inform the patient that a report of the results will be made available to the requesting health-care provider (HCP), who will discuss the results with the patient.
  • Recognize anxiety related to test results, and be supportive of impaired activity related to anticipated chronic pain resulting from joint inflammation, impairment in mobility, muscular deformity, and perceived loss of independence. Discuss the implications of abnormal test results on the patient’s lifestyle. Provide teaching and information regarding the clinical implications of the test results as appropriate. Explain the importance of physical activity in the treatment plan. Educate the patient regarding access to physical therapy, occupational therapy, and counseling services. Provide contact information, if desired, for the American College of Rheumatology ( or for the Arthritis Foundation ( Encourage the patient to take medications as ordered. Treatment with disease-modifying antirheumatic drugs (DMARDs) and biologic response modifiers may take as long as 2 to 3 mo to demonstrate their effects.
  • Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Answer any questions or address any concerns voiced by the patient or family.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy.

Related Monographs

  • Related tests include ANA, arthroscopy, BMD, bone scan, CBC, CRP, ESR, MRI musculoskeletal, radiography bone, RF, synovial fluid analysis, and uric acid.
  • Refer to the Immune and Musculoskeletal systems tables at the end of the book for related tests by body system.
Handbook of Laboratory and Diagnostic Tests, © 2013 Farlex and Partners
References in periodicals archive ?
Porphyromonas gingivalis causes periodontitis and may induce the production of RA-specific autoantibodies, anti-CCP antibodies.
(9) Schellekens et al (7) discovered RA-specific anticitrullinated peptide antibodies (anti-CCP antibodies) based on an enzyme-linked immunosorbent assay (ELISA) in 1998.
* Its confirm diagnosis should be accompanied by the determination of serum levels of anti-CCP Antibodies.
Conclusion: Most RA patients were positive for anti-CCP antibodies and presented with generalized gingivitis.
(10) In fact, combining the presence of anti-CCP antibodies and the presence of any of the individual RF isotypes in samples predating symptom onset results in a higher specificity, with increases to 99 percent and 100 percent, (6) providing a greater sense of confidence in the diagnosis.
A commercial second-generation enzyme-linked immunosorbent assay kit (Immunoscan RA anti-cyclic citrullinated peptide [anti-CCP] test kit; Euro Diagnostica, Malmo, Sweden) was used to detect anti-CCP antibodies, following manufacturer's instructions.
Number of Affected joints Serology patients 6 Wrists and shoulders are Five patients were the most commonly negative for RF and anti- involved joints CCP antibodies One patient was positive for RF and anti-CCP antibodies 2 Wrists, hands, TMJ, and Negative RF Negative shoulders anti-CCP 1 Hands, wrists, shoulders, Negative RF Anti-CCP and knees antibodies were not reported 1 Hands, knees, and feet Negative RF Anti-CCP antibodies were not reported 9 Hands, wrists, shoulders, Negative RF Anti-CCP and knees.
The clinical significance of the positive anti-CCP antibody titre without apparent manifestations of RA is not clear, but it has been proposed that patients with ILD and the presence of anti-CCP antibodies are at risk of developing RA (9).
According to the literature, anti-dsDNA and anti-CCP antibodies are found with high prevalence in rhupus syndrome (12).
ACPAs comprise a group of antibodies that are highly specific for the disease; among them are anti-CCP antibodies. The presence of high levels of anti-CCP at early diagnosis predicts more pronounced radiographic progression, as has been demonstrated by several studies [22-24].