Anti-citrullinated protein antibodies and their clinical utility in rheumatoid arthritis

Int J Rheum Dis. 2013 Aug;16(4):379-86. doi: 10.1111/1756-185X.12129. Epub 2013 Jul 15.


One of the most important serological discoveries in rheumatology in recent years has been the characterization of autoantigens in rheumatoid arthritis (RA) containing the amino acid citrulline. There are many citrullinated proteins in the inflamed RA synovium. Rheumatoid factor (RF), which is the immunologic hallmark of RA, is not specific for RA, as it is found in 5% of healthy individuals and in 10-20% of those over the age of 65 years. RFs are of low titer in early disease stages when a clear diagnosis is often not yet possible; But anti-citrullinated protein antibodies (ACPAs) can be found early in the disease course of RA, even years before the onset of clinical symptoms. The identification of citrullinated epitopes led to the development of the first and later second generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. Anti-CCP2 antibody has shown a specificity of 98% in sera from patients with established RA and 96% in sera from subjects with early RA. Anti-CCP can predict erosive disease, therefore could be a good serological marker for RA diagnosis.

Keywords: anti-citrullinated protein antibodies; anti-cyclic citrullinated peptides; autoantibodies; citrullinated proteins/peptides; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Antibodies, Anti-Idiotypic / blood*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / immunology*
  • Biomarkers / blood
  • Epitopes
  • Humans
  • Peptides, Cyclic / immunology*
  • Prognosis
  • Rheumatoid Factor / blood
  • Sensitivity and Specificity


  • Antibodies, Anti-Idiotypic
  • Biomarkers
  • Epitopes
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor