Cyclic Citrullinated Peptide (CCP):
A New Serum Marker for Rheumatoid Arthritis
More Specific than Rheumatoid Factor
Clinical Findings
Rheumatoid Arthritis (RA), a chronic inflammatory disorder of the synovial membranes, is one of the most common systemic autoimmune diseases. Approximately 1% of the world population is affected. The diagnosis of RA depends primarily on clinical manifestations, but laboratory results are helpful in differential diagnosis and disease management. Early diagnosis of RA is important both in disease treatment and management.1
Historically, rheumatoid factor (RF) has long been the serologic indicator for RA. However, it has been known for years that anti-keratin autoantibodies (AKA), also known as anti-perinuclear autoantibodies, are detected in 40-55% of RA patients2 and in 40-50% of clinically diagnosed RA patients who are RF negative.3,4 AKA is considered significantly more specific than RF. Additionally, AKA may precede the clinical appearance of RA by months or years.
Recently it was determined that AKA recognize an epitope that contains citrulline, the deiminated form of arginine.5 IgG antibodies against a synthetic peptide containing citrulline known as CCP (Cyclic Citrullinated Peptide) has proven to be superior to either AKA or RF testing in differentiating RA from other autoimmune diseases.6,7 The presence of CCP antibody occurs independently of elevated RF levels in patients with RA.
Table. Sensitivity and Specificity of CCP IgG ELISA Testing
(Data reported by INOVA Diagnostics, Inc. RA patients were diagnosed based on the ARA criteria.)
Patient Groups | No. | Number of Positive CCP IgG ELISA (%) |
Random Blood Donors | 216 | 2 (1%) |
Rheumatoid Arthritis | 252 | 193 (76%) |
RF + | 183 | 165 (90%) |
RF - | 69 | 28 (40%) |
Rheumatic Disease | 336 | 29 (8.6%) |
SLE | 103 | 10 (9.7%) |
Scleroderma | 86 | 10 (11.6%) |
Sjögren's Syndrome | 38 | 0 (0%) |
Other Rheumatic diseases | 109 | 9 (8.2%) |
Cryoglobulinemia | 29 | 2 (6.9%) |
Infectious disease | 87 | 2 (2.2%) |
Other patients | 29 | 1 (3.4%) |
Overall sensitivity of the anti-CCP test was 76% for RA; 90% sensitive for RF+ RA, and 40% sensitive for RF- RA. Specificity was 99% for healthy volunteers, 91% specific in rheumatic disease controls and 98% specific in infectious disease controls.
Indications for testing
- A clinical indication of RA but with negative or equivocal RF assays
- Presumed false positive RF (to investigate further possible RA)
- Monitoring disease activity and prognosis
- A presumptive diagnosis of patients considered at high risk
Methodology and Ordering Information are available from the Resource Guide
References
1. Kim JK and MH Weisman. When does rheumatoid arthritis begin and why do we need to know? Arthritis Rheum 2000; 43:473-84.
2. Vincent C et al. High diagnostic value in rheumatoid arthritis of antibodies to the stratum corneum of rat oesophageus epithelium, so-called 'antikeratin antibodies'. Ann Rheum Dis 1989; 48:712-22.
3. Corconnier C et al. Diagnostic value of anti-RA33 antibody, antikeratin antibody, antiperinuclear factor and antinuclear antibody in early rheumatoid arthritis: comparison with rheumatoid factor. Br J Rheumatol 1996; 35: 620-4.
4. Gabay C, Prieur AM, Meyer O. Occurrence of antiperinuclear, antikeratin, and anti-RA 33 antibodies in juvenile chronic arthritis. Ann Rheum Dis 1993; 52:785-9.
5. van Venrooj WJ. Citrullination: a small change for a protein with great consequences for rheumatoid arthritis. Arthritis Res 2000; 2:249-51.
6. Schellekens GA et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 2000; 43:155-63.
7.Bizzaro N et al. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clin Chem 2001; 47:1089-93.
Published in January, 2003