Anticitrulline antibodies (anti-CCP)

• antibodies to citrullinated proteins that show great specificity for rheumatoid arthritis (RA) and have the potential to indicate which patients are likely to have destructive joint disease (1)
  • citrulline is the product of post-translational modification of protein-bound arginine, catalysed by peptidylarginine deiminase (PAD)
    • there is a high specificity of antibodies to citrullinated proteins for RA - also an association to RA related joint damage
    • as well as occurring during the terminal differentiation of keratinocytes, citrullination occurs during cell death and injury
    • a reproducible and readily available assay has been developed to detect antibodies (anticyclic citrullinated peptide - anti-CCP)
    • anti-CCP antibodies are produced locally within the joint of RA patients
• use in RA
  • a very high proportion of patients with established RA have (predominately IgG) anti-CCP antibodies - up to 80% with RA are positive for anti-CCP. This compares with to finding anti-CCP in only 2-5% disease controls and 0-1% healthy controls
    • anti-CCP antibodies appear early in RA and can predate the clinical onset of disease by years - most, but not all, patients are also positive for RF
    • anti-CCP is associated with joint damage - this is the case even in those patients who are RF-negative. However anti-CCP is not associated with extraarticular features (unlike RF)
    • variation of levels with treatment of RA
      • the titre of anti-CCP does not fall with 'standard' anti-rheumatic therapy (unlike RF). There have however been reported significant falls in patients clinically responding to infliximab and to rituximab
    • anti-CCP has been reported to help distinguish between polymyalgia rheumatica and a polymyalgic onset of RA in elderly people
    • in children, anti-CCP has been reported in 13% of children with polyarticular juvenile idiopathic arthritis (JIA) (with an association with DR4 positivity and erosive joint disease) - however anti-CCP is only detected in about 2% of other types of JIA
    • anti-CCP has also been reported in 8-10% of patients with psoriatic arthritis - again associated with severe joint damage
    • anti-CCP occurs in approximately 7% of patients with primary Sjögren's, often at high titre - however not necessarily associated with erosive joint disease.
    • there is study evidence that anti-CCP predicts RA in patients presenting with an as yet undifferentiated arthritis
      • in this context anti-CCP has a sensitivity ranging from 45-65% but uniformly high specificity and high predictive value
      • the specificity of anti-CCP for diagnosing RA is higher than rheumatoid factor (2)

Reference:

1. ARC. Topical Reviews - Rheumatic Diseases: Serological Aids to Early Diagnosis. February 2006.
2. Nishimura K et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis.Ann Intern Med. 2007;146:797-808