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

Neil M. Ampel, Ian Robey, Chinh T. Nguyen, Brentin Roller, Jessica August, Kenneth S Knox, Demosthenes Pappagianis

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The 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-1β (IL-1β), interferon gamma (IFN-γ), IL-2, IL-13, and tumor necrosis factor alpha (TNF-α), were more than 10-fold above the levels seen without antigen stimulation. The levels of IFN-γ 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-γ, IL-2, and TNF-α have been previously noted, the finding of elevated levels of the innate cytokines GM-CSF and IL-1β could suggest that these, as well as IL-13, are early and specific markers for pulmonary coccidioidomycosis.

Original languageEnglish (US)
Article numbere00065-18
JournalmSphere
Volume3
Issue number3
DOIs
StatePublished - May 1 2018

Fingerprint

Coccidioidomycosis
Interleukin-13
Cytokines
Antigens
Lung
Interleukin-1
Interleukin-2
Interleukin-1alpha
Triazoles
Macrophage Colony-Stimulating Factor
Interleukin-1 Receptors
Granulocyte-Macrophage Colony-Stimulating Factor
Proteins
Tumor Necrosis Factor-alpha
Protein Array Analysis
Cellular Immunity
Interferon-gamma
Healthy Volunteers
Control Groups
Therapeutics

Keywords

  • Cellular immunity
  • Coccidioidomycosis
  • Cytokines

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

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. / Ampel, Neil M.; Robey, Ian; Nguyen, Chinh T.; Roller, Brentin; August, Jessica; Knox, Kenneth S; Pappagianis, Demosthenes.

In: mSphere, Vol. 3, No. 3, e00065-18, 01.05.2018.

Research output: Contribution to journalArticle

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abstract = "The 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-1β (IL-1β), interferon gamma (IFN-γ), IL-2, IL-13, and tumor necrosis factor alpha (TNF-α), were more than 10-fold above the levels seen without antigen stimulation. The levels of IFN-γ 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-γ, IL-2, and TNF-α have been previously noted, the finding of elevated levels of the innate cytokines GM-CSF and IL-1β could suggest that these, as well as IL-13, are early and specific markers for pulmonary coccidioidomycosis.",
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