Anti-CCP: Anti–Cyclic Citrullinated Peptide Antibody
- Also known as Anti-Citrullinated Protein Antibody (ACPA)
- Useful in diagnosis and prognosis of rheumatoid arthritis (RA)
- Newest anti-CCP assay yields a specificity of 98%, sensitivity of 80% for RA
- Present in 70% of patients with established RA
What is Anti-CCP?
- Anti-CCP antibodies are directed against citrullinated proteins
- Citrullination results from the post-translational modification (ie. not encoded in the original protein) of the amino acid arginine to citrulline by the enzyme peptidyl arginine deiminase
- Anti-CCP assays recognize a number of citullinated proteins
Role of Anti-CCP
- Anti-CCP antibodies are used in the diagnosis and prognosis of RA
- Can be seen years prior to RA onset and rarely develop after onset, suggesting that they are not just a consequence of inflammation.
- Associated with a more severe disease course and lower chance of drug-free remission.
Anti-CCP, HLA-DRB1 and the Shared Epitope
A number alleles of the HLA-DRB1 locus cause a predisposition to Anti-CCP+ RA.
HLA-DRB1 alleles encode one of the several 5 amino acid sequences that are grouped under the term Shared Epitope(SE). As part of the HLA molecule, the SE produces particular susceptibility to RA.
Hypotheses include a role for the SE in T-cell repertoire selection or antigen presentation; molecular mimicry of the SE by microbial proteins; and a potential pro-inflammatory signaling function that is unrelated to the role of the SE in antigen recognition.
The SE confers risk for more severe RA, as well as for the development of extra-articular manifestations.