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dc.contributor.authorAmpel, Neil M.
dc.contributor.authorRobey, Ian
dc.contributor.authorNguyen, Chinh T.
dc.contributor.authorRoller, Brentin
dc.contributor.authorAugust, Jessica
dc.contributor.authorKnox, Kenneth S.
dc.contributor.authorPappagianis, Demosthenes
dc.date.accessioned2018-09-04T20:14:15Z
dc.date.available2018-09-04T20:14:15Z
dc.date.issued2018
dc.identifier.citationAmpel NM, Robey I, Nguyen CT, Roller B, August J, Knox KS, Pappagianis D. 2018. Ex vivo cytokine release, determined by a multiplex cytokine assay, in response to coccidioidal antigen stimulation of whole blood among subjects with recently diagnosed primary pulmonary coccidioidomycosis. mSphere 3:e00065-18. https://doi.org/10.1128/ mSphere.00065-18.en_US
dc.identifier.issn2379-5042
dc.identifier.pmid29769377
dc.identifier.doi10.1128/mSphere.00065-18
dc.identifier.urihttp://hdl.handle.net/10150/628649
dc.description.abstractThe elements of the cellular immune response in human coccidioidomycosis remain undefined. We examined the ex vivo release of an array of inflammatory proteins in response to incubation with a coccidioidal antigen preparation to ascertain which of these might be associated with diagnosis and outcome. Patients with a recent diagnosis of primary pulmonary coccidioidomycosis and a control group of healthy subjects were studied. Blood samples were incubated for 18 h with T27K, a soluble coccidioidal preparation containing multiple glycosylated antigens, and the supernatant was assayed for inflammatory proteins using the multiplex Luminex system. The presentation and course of illness were compared to the levels of the inflammatory proteins. Among the 31 subjects studied, the median time from diagnosis to assay was 15 days. Of the 30 inflammatory proteins measured, the levels of only 7 proteins, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor alpha (IL-1RA), interleukin-1 beta (IL-1 beta), interferon gamma (IFN-gamma), IL-2, IL-13, and tumor necrosis factor alpha (TNF-alpha), were more than 10-fold above the levels seen without antigen stimulation. The levels of IFN-gamma and IL-2 were significantly elevated in those subjects not receiving triazole antifungal therapy compared to those who were receiving triazole antifungal therapy. While the levels of IL-1RA were nonspecifically elevated, elevated levels of IL-13 were seen only in those with active pulmonary coccidioidomycosis. Only six cytokines were specifically increased in subjects with recently diagnosed primary pulmonary coccidioidomycosis. While IFN-gamma, IL-2, and TNF-alpha have been previously noted, the finding of elevated levels of the innate cytokines GM-CSF and IL-1 beta could suggest that these, as well as IL-13, are early and specific markers for pulmonary coccidioidomycosis. IMPORTANCE Coccidioidomycosis, commonly known as Valley fever, is a common pneumonia in the southwestern United States. In this paper, we examined the release of 30 inflammatory proteins in whole-blood samples obtained from persons with coccidioidal pneumonia after the blood samples were incubated with a preparation made from the causative fungus, Coccidioides. We found that six of these proteins, all cytokines, were specifically released in high concentrations in these patients. Three of the cytokines were seen very early in disease, and an assay for all six might serve as a marker for the early diagnosis of Valley fever.en_US
dc.description.sponsorshipArizona Biomedical Research Commission of the State of Arizonaen_US
dc.language.isoenen_US
dc.publisherAMER SOC MICROBIOLOGYen_US
dc.relation.urlhttp://msphere.asm.org/lookup/doi/10.1128/mSphere.00065-18en_US
dc.rightsThis is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.en_US
dc.subjectcellular immunityen_US
dc.subjectcoccidioidomycosisen_US
dc.subjectcytokinesen_US
dc.titleCytokine Release, Determined by a Multiplex Cytokine Assay, in Response to Coccidioidal Antigen Stimulation of Whole Blood among Subjects with Recently Diagnosed Primary Pulmonary Coccidioidomycosisen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Div Infect Disen_US
dc.contributor.departmentUniv Arizona, Coll Med, Div Pulm Meden_US
dc.identifier.journalMSPHEREen_US
dc.description.noteOpen Access Journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitlemSphere
dc.source.volume3
dc.source.issue3
refterms.dateFOA2018-09-04T20:14:16Z


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