Cytokine signature associated with disease severity in chronic fatigue syndrome patients

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.

Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection

“…IFN-γ was the prominent cytokine marker separating short—from long-term patients, with network and recursive partitioning analyses describing the broader relationships between the immune markers tested, as well as age. Recent investigations of ME/CFS cytokine profiles have shown statistical significance for TGF-β and Resistin when compared to matched healthy controls, as well as significant correlations of seventeen cytokines with disease severity, with thirteen being pro-inflammatory [31]. …”

Human immunophenotyping via low-variance, low-bias, interpretive regression modeling of small, wide data sets: Application to aging and immune response to influenza vaccination

“…The complete list of features is provided in Appendix B of the online supplement. All cytokine features were detrended for nonspecific binding prior to analysis (Montoya et al, in preparation ). Volunteers' ages ranged from 19 years to 84 years with a mean age of ∼ 53 years, where, by design, sampling was stratified into two groups of a) young adults (19 to 28 years) and b) elderly (70 to 84 years).…”

A reboot for chronic fatigue syndrome research

“…In the past few years, researchers have revealed hints of an unusual immune response in ME/CFS. Most recently, last June, Montoya and his colleagues revealed 9 abnormalities in the levels of 17 immune-system proteins called cytokines in people with severe cases of the syndrome. What "LAST YEAR, I WENT TO 117 DOCTOR APPOINTMENTS AND PAID $18,000 IN OUT-OF-POCKET EXPENSES.…”