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. 2016 Mar 10;17:3.
doi: 10.1186/s12865-016-0142-3.

Illness Progression in Chronic Fatigue Syndrome: A Shifting Immune Baseline

Free PMC article

Illness Progression in Chronic Fatigue Syndrome: A Shifting Immune Baseline

Lindsey Russell et al. BMC Immunol. .
Free PMC article


Background: Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness.

Methods: Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18-50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori.

Results: Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75-88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years.

Conclusions: These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

Keywords: Chronic fatigue; Classification model; Cytokines; Immune signaling; Menopause and immunity.


Fig. 1
Fig. 1
Relative contribution to classification of ME/CFS subjects versus healthy control subjects across duration of illness for cytokines largely unaffected by age and BMI. Average value with standard error for the coefficients of IL-1α, IL-6 and IL-8 in a linear model for classification of ME/CFS subjects as estimated across 50 random subsets of n = 10 ME/CFS and n = 10 healthy control subjects sampled from subgroups of differing illness duration

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