Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis

Int J Tuberc Lung Dis. 2017 Mar 1;21(3):270-277. doi: 10.5588/ijtld.16.0351.

Abstract

Setting: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results.

Objective: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB.

Design: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests.

Results: Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI.

Conclusions: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cytokines / metabolism*
  • False Positive Reactions
  • Humans
  • Infant
  • Infant, Newborn
  • Interferon-gamma / metabolism
  • Interferon-gamma Release Tests / methods*
  • Interleukin-2 / metabolism
  • Latent Tuberculosis / diagnosis*
  • Mycobacterium tuberculosis / isolation & purification
  • Sensitivity and Specificity
  • Tuberculosis / diagnosis*

Substances

  • Cytokines
  • Interleukin-2
  • Interferon-gamma