Interferon-\u03b3 and CXCL10 responses related to complaints in patients with Q fever fatigue syndrome

Stephan P Keijmel,Chantal P Bleeker-Rovers,Marcel Van Deuren,Leo A B Joosten,Mihai G Netea,Teske Schoffelen,Anne F M Jansen,Jos W M Van Der Meer,Anja Scholzen,Ruud P H Raijmakers

doi:10.1007/s10096-018-3265-z

Abstract

Approximately 20% of patients with acute Q fever develop Q fever fatigue syndrome (QFS), a debilitating fatigue syndrome. This study further investigates the role of C. burnetii-specific IFNγ, but also IL-2, CXCL9, CXCL10, and CXLC11 production in QFS patients. C. burnetii-specific IFNy, IL-2, CXCL9, CXCL10, and CXCL11 production were tested in ex vivo stimulated whole blood of QFS patients who recovered from their complaints (n = 8), QFS patients with persisting complaints (n = 27), and asymptomatic Q fever seropositive controls (n = 10). With the exclusion of one outlier, stimulation with C. burnetii revealed significantly higher IFNy and CXCL10 production in QFS patients with persisting complaints (medians 288.0 and 176.0 pg/mL, respectively) than in QFS patients who recovered from their complaints (medians 93.0 and 85.5 pg/mL, respectively) (p = 0.041 and 0.045, respectively). No significant differences between groups were found for C. burnetii-specific IL-2, CXCL9, and CXCL11 production. These findings point towards a difference in cell-mediated immunity in QFS patients with persisting complaints compared to those who recovered from their complaints. Such a difference may aid to eventually diagnose QFS more objectively and might serve as an indicator of its underlying etiology.

Highlights

Q fever is a zoonotic disease caused by the Gram-negative intracellular bacterium Coxiella burnetii that occurs worldwide [1]
Stimulation with C. burnetii for 24 h yielded a median IFNγ production of 288 pg/mL for Q fever fatigue syndrome (QFS) patients with persisting complaints, 107 pg/mL for QFS patients who recovered from their complaints, and 267 pg/mL for asymptomatic Q fever seropositive controls, but showed no significant difference between groups
No significant difference in antigen-specific IFNγ and IL-2 production, and IFNγ/IL-2 ratio, was found between QFS patients and asymptomatic Q fever seropositive controls, or in antigen-specific IL-2, CXCL9, and CXCL11 production between QFS patients with persisting complaints and QFS patients who recovered from their complaints

Summary

Introduction

Q fever is a zoonotic disease caused by the Gram-negative intracellular bacterium Coxiella burnetii that occurs worldwide [1]. Human primary infection is thought to remain asymptomatic in approximately 60% of cases with the other 40% resulting in symptomatic infection. 20% of acute Q fever patients develop a prolonged state of debilitating postinfectious fatigue, called Q fever fatigue syndrome (QFS) [2,3,4]. During the Q fever outbreak in the Netherlands between 2007 and 2011, over 4000 acute Q fever cases were notified, and it is estimated that at least 32,200 people were infected [6]. Hundreds of patients have been diagnosed with QFS [6, 7]

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Results

Conclusion