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

Elkayam O, Segal R, Bendayan D, van Uitert R, Onnekink C, Pruijn GJ - Arthritis Res. Ther. (2010)

Bottom Line: 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.The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.ACPA may be found in patients with TB.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

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Correlation between reactivities with citrullinated and with corresponding arginine-containing peptides. The ELISA data for each pair of peptides are depicted for the 36 most highly reactive TB sera. Values for individual sera are connected by a line.
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Figure 2: Correlation between reactivities with citrullinated and with corresponding arginine-containing peptides. The ELISA data for each pair of peptides are depicted for the 36 most highly reactive TB sera. Values for individual sera are connected by a line.

Mentions: To demonstrate that individual patient sera are reactive with both the citrullinated and non-citrullinated peptides, the results for a selection of sera (the most highly reactive sera) are depicted in correlation diagrams in Figure 2. This indicates that most of the reactive TB sera indeed bind to these peptides irrespective of the presence of citrulline.


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

Elkayam O, Segal R, Bendayan D, van Uitert R, Onnekink C, Pruijn GJ - Arthritis Res. Ther. (2010)

Correlation between reactivities with citrullinated and with corresponding arginine-containing peptides. The ELISA data for each pair of peptides are depicted for the 36 most highly reactive TB sera. Values for individual sera are connected by a line.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875640&req=5

Figure 2: Correlation between reactivities with citrullinated and with corresponding arginine-containing peptides. The ELISA data for each pair of peptides are depicted for the 36 most highly reactive TB sera. Values for individual sera are connected by a line.
Mentions: To demonstrate that individual patient sera are reactive with both the citrullinated and non-citrullinated peptides, the results for a selection of sera (the most highly reactive sera) are depicted in correlation diagrams in Figure 2. This indicates that most of the reactive TB sera indeed bind to these peptides irrespective of the presence of citrulline.

Bottom Line: 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.The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.ACPA may be found in patients with TB.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus