Anti-CCP

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.