Novel T-cell assays for the discrimination of active and latent tuberculosis infection: the diagnostic value of PPE family

Mol Diagn Ther. 2015 Oct;19(5):309-16. doi: 10.1007/s40291-015-0157-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Biomarkers / blood
  • Diagnosis, Differential
  • Female
  • Humans
  • Interleukin-2 / blood*
  • Latent Tuberculosis / blood
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / immunology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Sensitivity and Specificity
  • T-Lymphocytes / immunology*
  • Young Adult

Substances

  • Bacterial Proteins
  • Biomarkers
  • Interleukin-2
  • PPE68 protein, Mycobacterium tuberculosis