title: Diagnosis of Coxiella burnetii infection: comparison of a whole blood interferon-gamma production assay and a Coxiella ELISPOT.
abstract: Diagnosis of ongoing or past infection with Coxiella burnetii, the causative agent of Q fever, relies heavily on serology: the measurement of C. burnetii-specific antibodies, reflecting the host's humoral immune response. However, cell-mediated immune responses play an important, probably even more relevant, role in infections caused by the intracellular C. burnetii bacterium. Recent studies have investigated interferon-gamma (IFN-γ) based assays, including a whole-blood IFN-γ production assay and a Coxiella enzyme-linked immunospot (Coxiella ELISPOT), as potential diagnostic tools for Q fever diagnosis. Both are in-house developed assays using stimulating antigens of different origin. The main objective of this study was to compare the test performance of the IFN-γ production assay and the Coxiella ELISPOT for detecting a cellular immune response to C. burnetii in Q fever patients, and to assess the correlation between both assays. To that end, both tests were performed in a well-defined patient group of chronic Q fever patients (n = 16) and a group of healthy seronegative individuals (n = 17). Among patients, both the Coxiella ELISPOT and the IFN-γ production assay detected positive response in 14/16. Among controls, none were positive in the Coxiella ELISPOT, whereas the IFN-γ production assay detected positive results in 1/17 and 3/17, when using Henzerling and Nine Mile as stimulating antigens, respectively. These results suggest the Coxiella ELISPOT has a somewhat higher specificity than the IFN-γ production assay when Nine Mile is used as antigen stimulus. The assays showed moderate correlation: the Spearman correlation coefficient r ranged between 0.37-0.60, depending on the antigens used. Further investigation of the diagnostic potential for C. burnetii infection of both assays is warranted.
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Teske
authors.initials: T
authors.lastname: Schoffelen
authors.affiliation: Department of Pulmonary Diseases, Diakonessenhuis Utrecht, Utrecht, The Netherlands.
authors.forename: Gijs J M
authors.initials: GJ
authors.lastname: Limonard
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Chantal P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.affiliation: Institute for Life Sciences, University of Applied Sciences, Utrecht, The Netherlands.
authors.forename: John J M
authors.initials: JJ
authors.lastname: Bouwman
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Marrigje
authors.initials: M
authors.lastname: Nabuurs-Franssen
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands; Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.affiliation: Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay / Q000379:methods*; D003381:Coxiella; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D007371:Interferon-gamma
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