Analysis of cellular and soluble profiles in QuantiFERON nonconverters, converters, and reverters in the Gambia

Immun Inflamm Dis. 2019 Dec;7(4):260-270. doi: 10.1002/iid3.269. Epub 2019 Aug 20.

Abstract

Background: Tuberculosis (TB) is the leading cause of death from a single infectious agent worldwide. The immune system is capable of clearing the pathogen before establishment of latent infection but the mechanisms for this are not yet understood.

Methods: This study analysed highly exposed household contacts (HHC) of TB index cases who were categorised according to QuantiFERON (QFT) results at recruitment and 6 months. Seventeen (17) QFT nonconverters, 14 QFT converters, 18 QFT reverters and 18 latent TB infection (LTBI) were analysed. Supernatants generated following QFT stimulation at both time-points were analysed using a 64-plex cytokine array. Flow cytometry was performed on QFT converters and nonconverters at baseline only.

Results: Interleukin-2 (IL-2), IL-5, IL-13, APRIL, IL-17A, IP-10, MIP-1ß, sIL-6rb, OPN, and sTNFR2 were all significantly higher in the QFT converters compared with nonconverters at baseline. Levels of interferon-α2 (IFN-α2) and IL-2 were significantly lower in QFT reverters compared with nonconverters at baseline. Analysis of Ag-specific IL-2 levels resulted in an area under the curve (AUC) of 0.93 (95% confidence interval [CI], 0.84-1.00) for QFT converters compared to nonconverters and an AUC of 0.80 (0.65-0.95) for QFT reverters compared with LTBI. Purified protein derivative (PPD)-specific CD4 + CD26 + IFN-γ + cells were significantly increased (P = .0007) in QFT nonconverters compared with QFT converters at baseline.

Conclusions: Our results provide insight into the underlying mechanisms of resistance to sustained Mycobacterium tuberculosis infection.

Keywords: QFT conversion; QFT reversion; Th17 cells; cytokines; inflammation; tuberculosis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cytokines* / blood
  • Cytokines* / immunology
  • Female
  • Gambia / epidemiology
  • Humans
  • Immunity, Cellular*
  • Latent Tuberculosis* / blood
  • Latent Tuberculosis* / epidemiology
  • Latent Tuberculosis* / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis* / immunology
  • Mycobacterium tuberculosis* / metabolism

Substances

  • Cytokines