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Illness progression in chronic fatigue syndrome: a shifting immune baseline.

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posted on 06.05.2016 by L Russell, G Broderick, R Taylor, H Fernandes, J Harvey, Z Barnes, A Smylie, F Collado, EG Balbin, BZ Katz, NG Klimas, MA Fletcher
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.

Funding

This work was funded by the Solve ME/CFS Initiative (previously CFIDS Association of America) grants to G Broderick (PI), BZ Katz and R Taylor; and by grants from the US National Institute of Health, including R01 HD043301- 05 (PI R Taylor), R01 AR057853 (PI NG Klimas), 2R56AI065723-08 (PI MA Fletcher), R21AA016635 (PI M.A. Fletcher), R21 A1099809 (PI MA Fletcher), 1R01NS090200-01 (PI MA Fletcher); and by the US Department of Veterans Affairs, Merit Award CSRD 4987.69 to NG Klimas.

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Publisher Statement

This is a copy of an article published in BMC Immunology © 2016 BioMed Central Publications. © Russell et al.

Publisher

BioMed Central

issn

1471-2172

Issue date

10/03/2016

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