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

Gordon Broderick1*, Ben Z Katz2, Henrique Fernandes1, Mary Ann Fletcher3, Nancy Klimas4, Frederick A Smith5, Maurice RG O’Gorman25, Suzanne D Vernon6 and Renee Taylor7

Author Affiliations

1 Division of Pulmonary Medicine, Department of Medicine, University of Alberta, WMC 2E4.41 WC Mackenzie Health Sciences Centre, 8440 112 Street, Edmonton, AB, T6G 2R7, Canada

2 Division of Infectious Diseases, Anne and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

3 Department of Medicine, University of Miami, Miami, FL, USA

4 Miami Veterans Affairs Medical Center, Miami, FL, USA

5 Department of Pathology, Feinberg School of Medicine, Northwestern, Chicago, IL, USA

6 CFIDS Association of America, Charlotte, NC, USA

7 Department of Occupational Therapy, University of Illinois at Chicago, Chicago, IL, USA

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Journal of Translational Medicine 2012, 10:191  doi:10.1186/1479-5876-10-191

Published: 13 September 2012



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.


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.


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.


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.

Cytokines; Infectious mononucleosis; Chronic fatigue; Classification model