Cytokine Signature Associated With Disease Severity in Chronic Fatigue Syndrome Patients

Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):E7150-E7158. doi: 10.1073/pnas.1710519114. Epub 2017 Jul 31.

Abstract

Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine's preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

Keywords: chronic fatigue syndrome; cytokines; immune monitoring; myalgic encephalomyelitis; severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokine CXCL1 / blood
  • Chemokine CXCL1 / immunology
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / immunology
  • Cytokines / blood*
  • Cytokines / immunology
  • Fatigue Syndrome, Chronic / blood*
  • Fatigue Syndrome, Chronic / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / immunology

Substances

  • Biomarkers
  • Chemokine CXCL1
  • Chemokine CXCL10
  • Cytokines
  • Transforming Growth Factor beta1