"Citrullinated peptide" is a synthetic peptide antigen used by manufacturors as the target antigen for the detection of patient autoantibodies to citrullinated antigens² (the RF serological test is generally considered to be more sensitive at 75-85% but less specific at 60-65%³). Anti-CCP was shown to be highly specific for seropositive rheumatoid arthritis (98%) utilizing a simple ELISA assay¹. Many rheumatologists are now (2006) testing for both anti-CCP & RF in an attempt to make an earlier specific diagnosis in cases of undifferentiated arthritis³. Furthermore, 35% of seronegative rheumatoid arthritis patients were anti-CCP positive. In addition, a recent study demonstrated anti-CCP antibodies in 70% of patients in the early stages of rheumatoid arthritis.

Older general tests are ESR and CRP. Anti-perinuclear antibody, anti-keratin antibody and anti-filaggrin antibody have also been shown to be highly specific for rheumatoid arthritis, but there are no commercial assays available for these tests for a variety of reasons. Recently, the above antibodies have been shown to be directed against citrullinated substrates.

Because of its high specificity, the anti-CCP test should be extremely useful in differentiating rheumatoid arthritis (RA) from other diseases that can be difficult to distinguish from RA because these diseases may have both (1) arthritis and (2) rheumatoid factor positivity as features of their diseases (SLE, Sjogren's syndrome, hepatitis C, parvoviral arthropathy, sarcoidosis, seronegative spondyloarthropathy and others).

"RDL, Inc. has recently conducted an in-house analysis on patients' sera stored at ­70 degrees C in our facility utilizing a commercial assay for anti-CCP. Our results demonstrate 98% specificity for anti-CCP in RA and a sensitivity of 62% in agreement with the results reported in the literature. We detected anti-CCP in only 2.5% of SLE and 5% of parvoviral arthritis. We failed to detect anti-CCP in all other disease categories...recognizing that small numbers of patients' sera were available for testing, i.e., sarcoid arthropathy and hepatitis C arthropathy. It therefore appears likely that the anti-CCP assay will prove to be extremely valuable in the diagnosis of rheumatoid arthritis, in the differential diagnosis of rheumatoid factor-positive disorders potentially confused with RA, in confirming a diagnosis of RA in seronegative polyarthritis and in the diagnosis of RA in early synovitis patients¹."

Potential false positives in some tested cases:

1. Parvoviral Arthropathy, 5%of cases
2. SLE, 2.5% of cases
3. Early Synovitis
4. Hepatitis C
5. Seronegative Inflammatory Arthropathy
6. Polymyalgia Rheumatica
7. Sarcoidosis
8. Spondyloarthropathy 0/19
9. Ankylosing Spondylitis
10. Psoriatic Arthritis
11. Reiter's Syndrome
12. Inflammatory Bowel Disease with Arthritis
13. Undifferentiated Spondyloarthropathy
14. Fibromyalgia
15. Remitting Seronegative Symmetrical Synovitis with Pitting Edema

References:

1. Schellekens GA, Visser H Ben, de Jong DAW: "The Diagnostic Properties of RA Antibodies Recognizing a Cyclic..." Rheumatism, 2000;43:144-163. (see RDL, Inc. website, educational area).
2. Carolyn Beck, EdD., 2006 CME flyer for UTHSC @ SA audio-conference CMEs.
3. Ellen Sullivan, "Rheumatoid Arthritis: Test for Anti-CCP Antibodies Joining RF Test as Key Diagnostic Tools", LABMEDICINE (ASCP) 37(1):17-19, Jan. 2006.