The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment

Arthritis Res Ther. 2010;12(1):R12. doi: 10.1186/ar2913. Epub 2010 Jan 25.


Introduction: Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.

Methods: Serum samples of 134 patients with untreated mycobacterium infections (122 TB, 12 nontuberculous mycobacterium) were tested for antibodies against both the citrullinated (Cit) and the non-citrullinated (Arg) form of 2 cyclic synthetic peptides. In 33 patients, a follow-up sample was tested six months after starting anti-mycobacterial drugs.

Results: A substantial proportion of patients with mycobacterial infections demonstrated antibodies against 0401Cit, 0401Arg, 0722Cit and 0722Arg. Fourteen patients demonstrated anti-0401Cit, 83 anti-0401Arg, 22 anti-0722Cit and 61 anti-0722Arg, while none of these antibodies were detected in the 20 healthy controls. All the patients but one, who were anti-0401Cit and anti-0722Cit positive, demonstrated reactivity against the respective Arg peptide. In the subset of 33 patients with a follow-up test six months after starting treatment, the mean levels of antibodies to 0401Cit, 0401Arg, 0722Cit and 0722Arg significantly decreased after treatment. All the patients who were anti-0401Cit and anti-0722Cit positive turned negative after treatment. The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.

Conclusions: ACPA may be found in patients with TB. In most of the cases, the reactivity is citrulline independent. A positive cyclic citrullinated peptide (CCP) test in these patients should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / therapeutic use
  • Autoantibodies / blood*
  • Citrulline / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / immunology
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic* / immunology
  • Proteins / immunology
  • Proteins / metabolism
  • Tuberculosis / blood*
  • Tuberculosis / complications
  • Tuberculosis / immunology*
  • Young Adult


  • Antitubercular Agents
  • Autoantibodies
  • Peptides, Cyclic
  • Proteins
  • cyclic citrullinated peptide
  • Citrulline