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

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.