Q-fever Fatigue Syndrome (QFS) - a relation with upper respiratory tract infections?

Up to 20% of patients that are diagnosed with acute Q fever will develop Q
fever fatigue syndrome (QFS), a state of prolonged fatigue that often coincides
with muscle ache, painful joints, headache, memory loss, loss of concentration,
and frequently recurring upper respiratory tract infections. The latter is an
interesting phenomenon that might be explained by the concept of trained
immunity. The theory behind trained immunity is that myeloid innate immune
cells can be epigenetically reprogrammed by (infectious) stimuli, making their
response to a second (infectious) stimulus more pro-inflammatory. Since
Coxiella burnetii is known to reside and divide in monocytes and macrophages,
it is likely that this bacterium is able to reprogram the epigenetic makeup of
these cells and induce trained immunity. Secondary stimuli such as viral
respiratory tract infections could then induce a more distinct pro-inflammatory
reaction, giving the patient the sensation of more frequently recurring and
more severe upper respiratory tract infections. We would like to investigate
this theory through in vitro and ex vivo models.

To see whether C. burnetii is able to induce epigenetic changes in monocytes,
resulting in a more distinct pro-inflammatory response to re-stimulation with
viral particles, to see whether these changes are present in circulating
monocytes of QFS patients and to see whether these changes can be reversed with
epigenetic drugs.

this experimental case control study will be performed at the Radboudumc,
Nijmegen. The duration of the study is 1 year. In total, 10-15 QFS-patients and
10-15 healthy controls will be recruited. The study will consist of three
modalities:

1. In vitro training experiments with C. burnetii, re-stimulating with several
viral particles.
- Measure monocyte cytokine concentrations upon re-stimulation with viral
particles and measure histone modification surrounding the promoter regions of
these cytokines.
2. Investigate the presence of set histone modifications in an ex vivo model
of QFS patients that experience frequent upper respiratory tract infections
since their acute Q-fever infection.
3. Investigate whether these histone modifications can be reversed with
epigenetic drugs in ex vivo models of QFS patients that experience frequent
upper respiratory tract infections since their acute Q-fever infection.

Burden:
- Collection of 7 tubes of EDTA blood (10ml) and for healthy controls 1 serum
tube (3.5mL).

Risks:
- No risks other than a local hematoma related to a single venous puncture.