Altered interferon-γ response in patients with Q-fever fatigue syndrome

J Infect. 2016 Apr;72(4):478-85. doi: 10.1016/j.jinf.2016.01.004. Epub 2016 Jan 25.


Objectives: Whether immunological mechanisms underlie Q-fever fatigue syndrome (QFS) remains unclear. For acute Q-fever, the antigen-specific interferon-γ (IFNγ) response may be a useful tool for diagnosis, and the IFNγ/interleukin(IL)-2 production ratio may be a marker for chronic Q-fever and treatment monitoring. Here we explored the specific IFNγ production and IFNγ/IL-2 ratio in QFS patients.

Methods: IFNγ and IL-2 production were tested in ex-vivo stimulated whole blood of QFS patients (n = 20), and compared to those previously determined in seropositive controls (n = 135), and chronic Q-fever patients (n = 28). Also, the correlation between patient characteristics and IFNγ, IL-2, and IFNγ/IL-2 ratio was determined.

Results: QFS patients were younger (p < 0.001), but gender distribution was similar to seropositive controls and chronic Q-fever patients. Coxiella burnetii Nine Mile stimulation revealed a higher IFNγ production in QFS (median 319.5 pg/ml) than in seropositive controls (120 pg/ml, p < 0.01), but comparable to chronic Q-fever (2846 pg/ml). The IFNγ/IL-2 ratio was similar to that in seropositive controls, but lower than in chronic Q-fever patients (p < 0.01). Symptom duration was positively correlated with IL-2 production, and negatively correlated with the IFNγ/IL-2 ratio.

Conclusions: These results point to an altered cell-mediated immunity in QFS, and suggest a different immune response than in chronic Q-fever.

Keywords: Cell-mediated immunity; Coxiella burnetii; Cytokines; Diagnosis; IFNγ; Interferon-gamma; Q-fever; Q-fever fatigue syndrome; QFS.

MeSH terms

  • Adult
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Case-Control Studies
  • Fatigue
  • Female
  • Humans
  • Immunity, Cellular / immunology
  • Interferon-gamma / blood
  • Interferon-gamma / immunology*
  • Interferon-gamma Release Tests
  • Interleukin-2 / blood
  • Interleukin-2 / immunology
  • Male
  • Middle Aged
  • Q Fever / blood
  • Q Fever / epidemiology*
  • Q Fever / immunology*
  • Young Adult


  • Antibodies, Bacterial
  • Interleukin-2
  • Interferon-gamma