Detection of interleukin-2 is not useful for distinguishing between latent and active tuberculosis in clinical practice: a prospective cohort study

Clin Microbiol Infect. 2016 Dec;22(12):1007.e1-1007.e5. doi: 10.1016/j.cmi.2016.09.004. Epub 2016 Sep 16.

Abstract

Objective: Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON®-TB Gold In-tube (QFT) after 72 h of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort.

Methods: A multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. Interferon-γ (IFN-γ) and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h of incubation. The accuracy of IL-2 for indicating latent TB infection (LTBI) was assessed by receiving operating characteristic curves. .

Results: Twenty-eight participants were not infected, 43 had LTBI, 69 had TB, and 21 were not classifiable. Median (interquartile range) IL-2 concentrations after 72 h of incubation were 0.0 pg/mL (0.0-0.0) in uninfected individuals, 261.0 pg/mL (81.0-853.0) in LTBI individuals, 166.5 pg/mL (33.5-551.5) in patients with extrapulmonary TB, 95.0 pg/mL (26.0-283.0) in patients with smear-negative pulmonary TB, and 38.5 pg/mL (7.5-178.0) in patients with smear-positive pulmonary TB (p <0.0001). The area under the curve of the receiving operating characteristic curve (95% CI) of IL-2 after 72 h of incubation for the diagnosis of LTBI was 0.63 (0.53-0.74) when all TB cases were considered as a single group, ranging from 0.59 (0.47-0.71) to 0.72 (0.58-0.85) when only extrapulmonary and smear-positive pulmonary TB cases respectively were considered.

Conclusions: Quantification of IL-2 in the supernatant of QFT after a prolonged incubation is not useful to distinguish between LTBI and active disease in clinical practice.

Keywords: Active tuberculosis; Interferon-γ; Interleukin-2; Latent tuberculosis infection; QuantiFERON.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-2 / blood*
  • Latent Tuberculosis / blood
  • Latent Tuberculosis / diagnosis*
  • Male
  • Middle Aged
  • Prospective Studies
  • Spain
  • Tuberculosis / blood
  • Tuberculosis / diagnosis*
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / diagnosis*

Substances

  • Biomarkers
  • IFNG protein, human
  • IL2 protein, human
  • Interleukin-2
  • Interferon-gamma