Patients with pulmonary tuberculosis are frequently positive for anti-cyclic citrullinated peptide antibodies, but their sera also react with unmodified arginine-containing peptide

Arthritis Rheum. 2008 Jun;58(6):1576-81. doi: 10.1002/art.23514.


Objective: The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) has high sensitivity and specificity for rheumatoid arthritis (RA). However, detection of anti-CCP in patients with active pulmonary tuberculosis (TB) has recently been reported. To determine whether this activity was specific for the citrullinated residue, the specificity of anti-CCP-positive sera for CCP versus that for unmodified arginine-containing peptide (CAP) was examined in patients with TB and compared with that in patients with RA.

Methods: Anti-CCP and anti-CAP in sera from patients with pulmonary TB (n = 49), RA patients (n = 36), and controls (n = 18) were tested by ELISA. Sera were available at diagnosis from most TB patients. All TB patients were treated with a combination of 2-4 antibiotics for at least 6 months, and sera were collected over time.

Results: Anti-CCP was found in 37% of TB patients and in 43% of RA patients. CAP reactivity was more common in TB than in RA. High anti-CCP:anti-CAP ratios (>2.0) were seen far more commonly in anti-CCP-positive RA patients than in anti-CCP-positive TB patients (94% versus 22%). Anti-CCP was inhibited by CCP peptide in sera from RA patients, but not in sera from TB patients. A slight increase in anti-CCP was common after initiating treatment for TB, although the anti-CCP level decreased after 1-2 months.

Conclusion: Anti-CCP is frequently present in patients with active TB. However, many anti-CCP-positive TB sera also reacted with CAP, and anti-CCP:anti-CAP ratios in TB sera were low. Anti-CCP:anti-CAP ratios should be useful clinically for distinguishing CCP-specific reactivity seen in RA from reactivity with both CCP and CAP frequently seen in pulmonary TB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Specificity*
  • Arginine / immunology*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Biomarkers / blood
  • Case-Control Studies
  • Humans
  • Peptides, Cyclic / immunology*
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / immunology*


  • Biomarkers
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Arginine