TNF-α/IL-2 ratio discriminates latent from active tuberculosis in immunocompetent children: a pilot study

Pediatr Res. 2012 Oct;72(4):370-4. doi: 10.1038/pr.2012.89. Epub 2012 Jul 13.


Background: Distinguishing latent tuberculosis (LTB) from tuberculosis (TB) disease may be challenging in children. Here, we analyzed cytokine profiles that can distinguish the two infection stages in a nonendemic country (France).

Methods: Immunocompetent children with LTB (n = 6) or TB disease (n = 8) (median age: 6.2 and 5.7 years, respectively) were analyzed. Four young uninfected children were included as controls. A Luminex assay evaluated cytokine responses to Mycobacterium tuberculosis antigens.

Results: Poor interleukin-4 (IL-4) and IL-10 responses precluded analysis of these cytokines. Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-2, and T-helper type 1 (Th1) cytokines and IL-5, IL-13, T-helper type 2 (Th2) cytokines were simultaneously induced by antigens in 14/14 infected but 0/4 uninfected children. Th1 cytokine levels were similar in LTB and TB disease: IFN-γ: 12,254 and 10,495 pg/ml; IL-2: 2,097 and 1,869 pg/ml; and TNF-α: 1,020 and 2,875 pg/ml, respectively. Th2 cytokine levels were similar and even higher in LTB than in TB disease: IL-5: 23 and 10 pg/ml; IL-13: 284 and 109 pg/ml, respectively. Positive correlation of cytokine levels, whether Th1 or Th2, was observed. Higher (P = 0.008) TNF-α/IL-2 ratios distinguished 6/8 active TB disease cases from 6/6 LTB cases.

Conclusion: TNF-α/IL-2 ratio may discriminate TB disease from LTB in immunocompetent children. Larger studies in TB endemic settings must verify these results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunocompetence*
  • Immunologic Tests*
  • Infant
  • Interferon-gamma Release Tests
  • Interleukin-2 / blood*
  • Latent Tuberculosis / blood
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / immunology
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / isolation & purification
  • Pilot Projects
  • Predictive Value of Tests
  • Prospective Studies
  • Sputum / microbiology
  • Tuberculin Test
  • Tuberculosis / blood
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology
  • Tumor Necrosis Factor-alpha / blood*


  • Biomarkers
  • IL2 protein, human
  • Interleukin-2
  • Tumor Necrosis Factor-alpha