Novel T-Cell Assays for the Discrimination of Active and Latent Tuberculosis Infection: The Diagnostic Value of Ppe Family Publisher Pubmed



Pourakbari B¹ ; Mamishi S^{1, 2} ; Marjani M³ ; Rasulinejad M⁴ ; Mariotti S⁵ ; Mahmoudi S¹
Source: Molecular Diagnosis and Therapy Published:2015

Abstract

Objective: The diagnosis of active and latent tuberculosis remains a challenge. Although a new approach based on detecting Mycobacterium tuberculosis-specific T-cells has been introduced, it cannot distinguish between latent infection and active disease. The aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). Method: The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. Results: The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 [95 % confidence interval (CI) 0.72–0.97] for LTBI diagnosis and 0.75 (95 % CI 0.63–0.89) for active TB diagnosis, respectively. Applying the 6.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78 %, specificity of 83 %, PPV of 83 % and NPV of 78 % for the discrimination of active TB and LTBI. In addition, a sensitivity of 81 %, specificity of 71 %, PPV of 68 and 83 % of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. Conclusion: This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and active TB disease. © 2015, Springer International Publishing Switzerland.