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Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

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posted on 06.12.2013, 00:00 authored by Gordon Broderick, Ben Z. Katz, Henrique Fernandes, Mary Ann Fletcher, Nancy Klimas, Frederick A. Smith, Maurice RG O’Gorman, Suzanne D. Vernon, Renee Taylor
Background: As Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Methods: Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Results: Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. Conclusion: These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

Funding

This analysis was funded by the CFIDS Association of America grants to G Broderick, BZ Katz and NG Klimas; cohort recruitment and assessment was supported by grants from the US National Institute of Health, including R01 HD043301-05 (PI R Taylor), R21AA016635 (PI M.A. Fletcher) and R01AI065723 (PI MA Fletcher); and R01AI065723 (PI MA Fletcher); the US Department of Veterans Affairs, Merit Award to NG Klimas.

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Publisher Statement

© 2012 Broderick et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Citation

Broderick, G. Katz, B. Z. Fernandes, H. Fletcher, M. A. Klimas, N. Smith, F. A. O'Gorman, M. R. G. Vernon, S. D. Taylor, R. Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue. Journal of Translational Medicine. Sep 2012;10. DOI: 10.1186/1479-5876-10-191

Publisher

BioMed Central

Language

en_US

issn

1479-5876

Issue date

01/09/2012

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