title: Altered interferon-γ response in patients with Q-fever fatigue syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: Radboud Expertise Centre for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Stephan.Keijmel@radboudumc.nl.
authors.forename: Stephan P
authors.initials: SP
authors.lastname: Keijmel
authors.affiliation: Radboud Expertise Centre for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Ruud.Raijmakers@radboudumc.nl.
authors.forename: Ruud P H
authors.initials: RP
authors.lastname: Raijmakers
authors.affiliation: Radboud Expertise Centre for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Chantal.Bleeker-Rovers@radboudumc.nl.
authors.forename: Chantal P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.affiliation: Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Jos.vanderMeer@radboudumc.nl.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Mihai.Netea@radboudumc.nl.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Radboud Expertise Centre for Q Fever, Department of Internal Medicine, Division of Infectious Diseases, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands; Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Teske.Schoffelen@radboudumc.nl.
authors.forename: Teske
authors.initials: T
authors.lastname: Schoffelen
authors.affiliation: Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Marcel.vanDeuren@radboudumc.nl.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D005221:Fatigue; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D059425:Interferon-gamma Release Tests; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011778:Q Fever / Q000097:blood / Q000453:epidemiology* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Cell-mediated immunity; Coxiella burnetii; Cytokines; Diagnosis; IFNγ; Interferon-gamma; Q-fever; Q-fever fatigue syndrome; QFS