Stephan P Keijmel1, Ruud P H Raijmakers2, Chantal P Bleeker-Rovers3, Jos W M van der Meer4, Mihai G Netea5, Teske Schoffelen6, Marcel van Deuren7. 1. 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. 2. 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. 3. 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. 4. Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Jos.vanderMeer@radboudumc.nl. 5. Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Mihai.Netea@radboudumc.nl. 6. 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. 7. Department of Internal Medicine, Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Electronic address: Marcel.vanDeuren@radboudumc.nl.
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. 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.
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-feverpatients (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-feverpatients. 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-feverpatients (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: Jonas Blomberg; Carl-Gerhard Gottfries; Amal Elfaitouri; Muhammad Rizwan; Anders Rosén Journal: Front Immunol Date: 2018-02-15 Impact factor: 7.561
Authors: Ruud P H Raijmakers; Anne F M Jansen; Stephan P Keijmel; Teske Schoffelen; Anja Scholzen; Jos W M van der Meer; Leo A B Joosten; Mihai G Netea; Marcel van Deuren; Chantal P Bleeker-Rovers Journal: Eur J Clin Microbiol Infect Dis Date: 2018-05-26 Impact factor: 3.267
Authors: Ruud P H Raijmakers; Anne F M Jansen; Stephan P Keijmel; Rob Ter Horst; Megan E Roerink; Boris Novakovic; Leo A B Joosten; Jos W M van der Meer; Mihai G Netea; Chantal P Bleeker-Rovers Journal: J Transl Med Date: 2019-05-14 Impact factor: 5.531
Authors: Ruud P H Raijmakers; Anne F M Jansen; Stephan P Keijmel; Jos W M van der Meer; Leo A B Joosten; Mihai G Netea; Chantal P Bleeker-Rovers Journal: Eur J Immunol Date: 2019-05-09 Impact factor: 5.532
Authors: Ruud P H Raijmakers; Megan E Roerink; Anne F M Jansen; Stephan P Keijmel; Ranko Gacesa; Yang Li; Leo A B Joosten; Jos W M van der Meer; Mihai G Netea; Chantal P Bleeker-Rovers; Cheng-Jian Xu Journal: J Transl Med Date: 2020-11-26 Impact factor: 5.531