title: A combination of interferon-gamma and interleukin-2 production by Coxiella burnetii-stimulated circulating cells discriminates between chronic Q fever and past Q fever.
abstract: Infection with Coxiella burnetii may lead to life-threatening chronic Q fever endocarditis or vascular infections, which are often difficult to diagnose. The present study aims to investigate whether measurement of in-vitro interferon-gamma (IFN-γ) production, a key cytokine in the immune response against C. burnetii, differentiates chronic from a past cleared infection, and whether measurement of other cytokines would improve the discriminative power. First, C. burnetii-specific IFN-γ production was measured in whole blood of 28 definite chronic Q fever patients and compared with 135 individuals with past Q fever (seropositive controls) and 908 seronegative controls. IFN-γ production was significantly higher in chronic Q fever patients than in controls, but with overlapping values between patients and seropositives. Secondly, the production of a series of other cytokines was measured in a subset of patients and controls, which showed that interleukin (IL)-2 production was significantly lower in patients than in seropositive controls. Subsequently, measuring IL-2 in all patients and all controls with substantial IFN-γ production showed that an IFN-γ/IL-2 ratio >11 had a sensitivity and specificity of 79% and 96%, respectively, to diagnose chronic Q fever. This indicates that a high IFN-γ/IL-2 ratio is highly suggestive for chronic Q fever. In an additional group of 25 individuals with persistent high anti-Coxiella phase I IgG titres without definite chronic infection, all but six showed an IFN-γ/IL-2 ratio <11. In conclusion, these findings hold promise for the often difficult diagnostic work-up of Q fever and the IFN-γ/IL-2 ratio may be used as an additional diagnostic marker.
authors.affiliation: Department of Internal Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Schoffelen
authors.forename: T
authors.initials: T
authors.lastname: Sprong
authors.forename: C P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.forename: M C A
authors.initials: MC
authors.lastname: Wegdam-Blans
authors.forename: A
authors.initials: A
authors.lastname: Ammerdorffer
authors.forename: M J H
authors.initials: MJ
authors.lastname: Pronk
authors.forename: Y E P
authors.initials: YE
authors.lastname: Soethoudt
authors.forename: M E E
authors.initials: ME
authors.lastname: van Kasteren
authors.forename: T
authors.initials: T
authors.lastname: Herremans
authors.forename: H A
authors.initials: HA
authors.lastname: Bijlmer
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: J W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: L A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: M
authors.initials: M
authors.lastname: van Deuren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D016997:Coxiella burnetii / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011778:Q Fever / Q000175:diagnosis* / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: C573415:IFNG protein, human; C508594:IL2 protein, human; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Chronic Q fever; Coxiella burnetii; cytokines; diagnosis; interferon-gamma; interleukin-2