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Overview Testing for Rheumatoid Arthritis using CCP Antigen
Rheumatoid Arthritis (RA) is one of the most common systemic autoimmune diseases, affecting approximately 0.5% of the world population.¹ A diagnosis of RA still primarily depends on clinical manifestations of the disease. Until recently, the only serological test routinely used in the diagnosis of RA was the determination of the presence of rheumatoid factor (RF), found in approximately 50%-90% of these patients.^1,2 However, RF is also found in people with infections, other autoimmune diseases and also in some healthy individuals.^1,2

It is important for disease management to diagnose and treat individuals with RA as early as possible.³ It has been known for many years that anti-perinuclear autoantibodies, which are also called anti-keratin autoantibodies, are found in people with RA.⁴ Several years ago it was discovered that these antibodies recognize an epitope (an antibody binding site) that contains the deimidated form of arginine called citrulline.^5,6 A circular peptide containing citrulline, called CCP (Cyclic Citrullinated Peptide), was found to be better at discriminating RA patients from other rheumatic patients than either the perinuclear antibody test or the tests for rheumatoid factor.^4,7,8 In a review of the published literature⁶, 77% of patients with RA are positive for anti-CCP, while an average of 3% of non-RA subjects are positive.

Over the years, further clinical use, research and refinement has dramatically improved the utility of the CCP peptide as new generations of peptide have been developed.^6,9 The latest peptide, CCP3 shows a 5% increase in sensitivity at detecting RA patients than the previous widely-marketed peptide ^4,7,8 suggesting that additional epitopes were not available in the previous generation CCP antigen.

1. Wener MH: Rheumatoid Factors. Manual of Clinical Laboratory Immunology, NR Rose et al eds, American Society for Microbiology Press, 961-972 (2002).

2. Borretzen M et al: Rheumatoid Factors. Autoantibodies, Peter JB and Shoenfeld Y, eds, Elsevier Science B.V., 706-715 (1996).

3. Kim JK and Weisman MH: When does rheumatoid arthritis begin and why do we need to know? Arthritis Rheum 43: 473-484 (2000).

4. van Jaarsveld CHM et al: The prognostic value of the antiperinuclear factor, anti-citrullinated peptide antibodies and rheumatoid factor in early arthritis. Clin Exp Rheum 17: 1689-1697 (1999).

5. Vossenaar ER and Van Venrooj WJ: Anti-CCP antibodies, a highly specific marker for (early) rheumatoid arthritis. Clin Applied Immunol Rev 4: 239-262 (2004).

6. Schellekens GA et al: Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 101: 273-281 (1998).

7. Vittecoq O et al: Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis. Clin Exp Immunol 135: 173-180 (2004).

8. Saraux A et al: Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis. J Rheumatol 30: 2535-2539 (2003).

9. Vencovsky J et al. Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis 62: 427-430 (2003).

10. van Gaalen FA et al: A comparison of the diagnostic accuracy and prognostic value of the first- and second anti-cyclic citrullinated peptide autoantibody (CCP1 and CCP2) tests for rheumatoid arthritis. Ann Rheum Dis epub ahead of print (2005).