A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome

Anne Liese Smylie, Gordon Broderick, Henrique Fernandes, Shirin Razdan, Zachary Barnes, Fanny Collado, Connie Sol, Mary Ann Fletcher, Nancy Klimas

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female).Methods: Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group.Results: Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.Conclusions: Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.

Original languageEnglish
Article number29
JournalBMC Immunology
Volume14
Issue number1
DOIs
StatePublished - Jun 25 2013
Externally publishedYes

Fingerprint

Gulf War
Chronic Fatigue Syndrome
Exercise
Interleukin-23
Interleukin-17
Cytokines
Interleukin-10
Interleukin-15
Interleukin-5
Veterans
Interleukin-12
Antigen-Antibody Complex
Exercise Test
Interleukin-4
Interleukin-2
Linear Models

Keywords

  • Chronic fatigue
  • Classification model
  • Cytokines
  • Exercise challenge
  • Gulf war illness
  • Immune signaling

ASJC Scopus subject areas

  • Immunology

Cite this

Smylie, A. L., Broderick, G., Fernandes, H., Razdan, S., Barnes, Z., Collado, F., ... Klimas, N. (2013). A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunology, 14(1), [29]. https://doi.org/10.1186/1471-2172-14-29

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. / Smylie, Anne Liese; Broderick, Gordon; Fernandes, Henrique; Razdan, Shirin; Barnes, Zachary; Collado, Fanny; Sol, Connie; Fletcher, Mary Ann; Klimas, Nancy.

In: BMC Immunology, Vol. 14, No. 1, 29, 25.06.2013.

Research output: Contribution to journalArticle

Smylie, AL, Broderick, G, Fernandes, H, Razdan, S, Barnes, Z, Collado, F, Sol, C, Fletcher, MA & Klimas, N 2013, 'A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome', BMC Immunology, vol. 14, no. 1, 29. https://doi.org/10.1186/1471-2172-14-29
Smylie AL, Broderick G, Fernandes H, Razdan S, Barnes Z, Collado F et al. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunology. 2013 Jun 25;14(1). 29. https://doi.org/10.1186/1471-2172-14-29
Smylie, Anne Liese ; Broderick, Gordon ; Fernandes, Henrique ; Razdan, Shirin ; Barnes, Zachary ; Collado, Fanny ; Sol, Connie ; Fletcher, Mary Ann ; Klimas, Nancy. / A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. In: BMC Immunology. 2013 ; Vol. 14, No. 1.
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abstract = "Background: Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female).Methods: Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group.Results: Classification accuracies in excess of 80{\%} were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.Conclusions: Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.",
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