Anti-cyclic citrullinated peptide (CCP) antibodies in patients with long-standing rheumatoid arthritis and their relationship with extra-articular manifestations

Clin Biochem. 2006 Oct;39(10):961-5. doi: 10.1016/j.clinbiochem.2006.06.004. Epub 2006 Jul 13.


Objectives: To evaluate frequency of anti-cyclic citrullinated peptide antibodies (anti-CCP) in long-standing rheumatoid arthritis (LsRA) patients and their relationship with extra-articular manifestations of rheumatoid arthritis (RA), in addition to comparing frequency of anti-CCP antibodies in early RA (ERA) and LsRA group.

Design and methods: One hundred and fifteen consecutive RA patients were included in the study as having LsRA because their disease duration was longer than 3 years. Thirty-nine consecutive patients with RA were included in the study as having ERA (<3 years). Also, 64 individuals were included in the study as healthy controls to verify the specificity and sensitivity of anti-CCP antibodies. Anti-CCP antibody and rheumatoid factor (RF) were evaluated with enzyme-linked immunosorbent assay kits and standard nephelometry methods, respectively. Extra-articular manifestations were diagnosed by relevant criteria.

Results: The total number of patients with extra-articular manifestations was found to be 45 (39%). No significant difference was found between LsRA group and ERA group in terms of extra-articular manifestations. There were no differences between both groups regarding the number of patients with positive anti-CCP antibodies and the levels of anti-CCP antibodies. In LsRA group, there was a positive correlation between erosion and disease duration (r=0.24, p<0.01), between erosion and RF (r=0.29, p<0.002), and between erosion and anti-CCP antibody (r=0.21, p<0.02). Positive correlations between RF and anti-CCP antibody (r=0.32, p<0.0001), as well as between subcutaneous nodule and lung involvement (r=0.24, p<0.008), were found in the LsRA group. However, no positive correlation could be found between anti-CCP antibody positivity and extra-articular organ involvement, either cumulatively or separately.

Conclusions: Although anti-CCP antibodies are associated with the severity of the disease and erosion, they do not seem to have much linkage with extra-articular manifestations of RA.

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Sensitivity and Specificity


  • Autoantibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide