The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment.
BACKGROUND
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.
Elkayam
Ori
O
Department of Internal Medicine F and the Department of Rheumatology, Tel Aviv Medical Center and The Sackler Faculty of Medicine, Tel Aviv University, 6 Weizman Street, Tel Aviv 64239, Israel. oribe14@netvision.net.il
Segal
Refael
R
Bendayan
Daniele
D
van Uitert
Robert
R
Onnekink
Carla
C
Pruijn
Ger Jm
GJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D002956:Citrulline / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000097:blood* / Q000150:complications / Q000276:immunology*; D055815:Young Adult
D000995:Antitubercular Agents; D001323:Autoantibodies; D010456:Peptides, Cyclic; D011506:Proteins; C487763:cyclic citrullinated peptide; D002956:Citrulline