Evaluation of the potential diagnostic value of cytotoxic T lymphocyte-associated antigen-4 in differentiation of active and latent tuberculosis infection

Abstract

Objective To analyze the expressions of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the peripheral blood of patients with active tuberculosis (ATB) or latent tuberculosis infection (LTBI), and to evaluate its diagnostic value in differentiation of ATB and LTBI. Methods Forty-eight patients including 18 ATB cases and 30 LTBI cases were continuously enrolled from Wuxi No.5 People′s Hospital and Huashan Hospital affiliated to Fudan University from January 2011 to March 2013. Flow cytometry was applied to detect the CTLA-4 expression in CD4+ CD25+ FoxP3+ T cells in the peripheral blood of the 48 subjects. CTLA-4 levels were compared using non-parametric Mann-Whitney U test. Results The median percentage of CTLA-4+ Treg in CD4+ CD25+ Foxp3+ Treg cells of ATB patients was 18.95% (quantile range: 13.86%, 27.73%), and that in LTBI patients was 6.67% (quantile range: 5.74%, 9.59%), which was statistically significant (U=18.0, P<0. 01). Receiver operating curve (ROC) based on the CTLA-4 expression indicated that the area under the curve was 0.96, with the optimum cut-off value of 13.25%. Thus, the sensitivity and specificity for the diagnosis of ATB were 86.7% and 94.4%, respectively. Conclusion CTLA-4 has highly sensitivity and specificity for the differential diagnosis of ATB and LTBI whose interferon-gamma releasing assays are all positive, which may also provide meaningful clue for the study of pathogenesis of ATB. Key words: CTLA-4; Active tuberculosis; Latent tuberculosis infection; Differential diagnosis