Research Highlights:

• We explored the specific IFNγ production, and the IFNγ/IL-2 ratio in QFS patients.
• QFS patients have a significant higher IFNγ production than seropositive controls.
• The IFNγ/IL-2 ratio is significantly lower in QFS than in chronic Q-fever patients.
• These results point to an altered cell-mediated immunity in QFS.

Research abstract:

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. C. 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.

Altered interferon-γ response in patients with Q-fever fatigue syndrome, by Keijmel SP, Raijmakers RP, Bleeker-Rovers CP, van der Meer JW, Netea MG, Schoffelen T, van Deuren M. in J Infect. 2016 Jan 25. pii  [Epub ahead of print]