Boosting effect of IL-7 in interferon gamma release assays to diagnose Mycobacterium tuberculosis infection

PLoS One. 2018 Aug 29;13(8):e0202525. doi: 10.1371/journal.pone.0202525. eCollection 2018.

Abstract

Background: A quarter of the world's population is estimated to be infected with Myobacterium tuberculosis (Mtb). Infection is detected by immune response to M. tuberculosis antigens using either tuberculin skin test (TST) and interferon gamma release (IGRA's), tests which have low sensitivity in immunocompromised. IL-7 is an important cytokine for T-cell function with potential to augment cytokine release in in-vitro assays. This study aimed to determine whether the addition of IL-7 in interferon-gamma release assays (IGRAs) improves its diagnostic performance of Mtb infection.

Methods: 44 cases with confirmed TB and 45 household contacts without TB were recruited and 1ml of blood was stimulated in two separate IGRA's tube set: one set of standard Quantiferon TB gold tubes mitogen, TB antigen and TB Nil; one set of customized Quantiferon TB gold tubes with added IL-7. Following IFN-γ and IP-10 release was determined using ELISA.

Results: We found that the addition of IL-7 led to significantly higher release of IFN-γ in individuals with active TB from 4.2IU/ml (IQR 1.4-6.9IU/ml) to 5.1IU/ml (IQR 1.5-8.1IU/ml, p = 0.0057), and we found an indication of a lower release of both IFN-γ and IP-10 in participants with negative tests.

Conclusions: In TB cases addition of IL-7 in IGRA tubes augments IFN-γ but not IP-10 release, and seems to lower the response in controls. Whether IL-7 boosted IGRA holds potential over standard IGRA needs to be confirmed in larger studies in high and low TB incidence countries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / isolation & purification
  • Chemokine CXCL10 / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Interferon-gamma / immunology*
  • Interferon-gamma Release Tests
  • Interleukin-7 / immunology
  • Interleukin-7 / pharmacology*
  • Male
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • T-Lymphocytes / immunology
  • T-Lymphocytes / microbiology
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology
  • Tuberculosis / microbiology

Substances

  • Antigens, Bacterial
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Interleukin-7
  • Mycobacterium tuberculosis antigens
  • Interferon-gamma

Grants and funding

This work was supported by funding from the Rudolf Geigy Foundation (Basel, Switzerland) and the Statens Serum Institute (Copenhagen, Denmark). Morten Ruhwald received funding from European Commission H2020 program [grant number TBVAC2020 643381] and Research Council Norway [GLOBVAC 248042/H10]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.