Whole Blood Interferon γ Release Is a More Sensitive Marker of Prior Exposure to Coxiella burnetii Than Are Antibody Responses

Front Immunol. 2021 Jul 28:12:701811. doi: 10.3389/fimmu.2021.701811. eCollection 2021.

Abstract

For the zoonotic disease Q fever, serological analysis plays a dominant role in the diagnosis of Coxiella burnetii infection and in pre-screening for past exposure prior to vaccination. A number of studies suggest that assessment of C. burnetii-specific T-cell IFNγ responses may be a more sensitive tool to assess past exposure. In this study, we assessed the performance of a whole blood C. burnetii IFNγ release assay in comparison to serological detection in an area of high Q fever incidence in 2014, up to seven years after initial exposure during the Dutch Q fever outbreak 2007-2010. In a cohort of >1500 individuals from the Dutch outbreak village of Herpen, approximately 60% had mounted IFNγ responses to C. burnetii. This proportion was independent of the Coxiella strain used for stimulation and much higher than the proportion of individuals scored sero-positive using the serological gold standard immunofluorescence assay. Moreover, C. burnetii-specific IFNγ responses were found to be more durable than antibody responses in two sub-groups of individuals known to have sero-converted as of 2007 or previously reported to the municipality as notified Q fever cases. A novel ready-to-use version of the IFNγ release assay assessed in a subgroup of pre-exposed individuals in 2021 (10-14 years post exposure) proved again to be more sensitive than serology in detecting past exposure. These data demonstrate that C. burnetii-induced IFNγ release is indeed a more sensitive and durable marker of exposure to C. burnetii than are serological responses. In combination with a simplified assay version suitable for implementation in routine diagnostic settings, this makes the assessment of IFNγ responses a valuable tool for exposure screening to obtain epidemiological data, and to identify previously exposed individuals in pre-vaccination screens.

Keywords: Coxiella burnetii; Q fever; T-cell; biomarker; diagnostic test; exposure; human; interferon gamma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology*
  • Antibody Formation / immunology*
  • Biomarkers / blood*
  • Coxiella burnetii / immunology*
  • Cross-Sectional Studies
  • Humans
  • Interferon-gamma / blood*
  • Interferon-gamma / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / microbiology
  • Q Fever / blood
  • Q Fever / immunology
  • Q Fever / microbiology
  • Zoonoses / blood
  • Zoonoses / immunology
  • Zoonoses / microbiology

Substances

  • Antibodies, Bacterial
  • Biomarkers
  • Interferon-gamma