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

Taylor, Smith, Broderick Gordon, Katz, Fernandes Henrique, Fletcher Mary, Klimas Nancy, O’Gorman, Vernon, Taylor Renee

Description

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.

Sujets

• Cytokine
• Infectious mononucleosis
• Chronic fatigue syndrome

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 18
• Langue: English

Extrait

Brodericket al. Journal of Translational Medicine2012,10:191 http://www.translationalmedicine.com/content/10/1/191

R E S E A R C HOpen Access Cytokine expression profiles of immune imbalance in postmononucleosis chronic fatigue 1* 21 34 5 Gordon Broderick, Ben Z Katz , Henrique Fernandes , Mary Ann Fletcher , Nancy Klimas , Frederick A Smith , 2,5 67 Maurice RG O’Suzanne D Vernonand Renee TaylorGorman ,

Abstract 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αand TNFβin 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γalso 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. Keywords:Cytokines, Infectious mononucleosis, Chronic fatigue, Classification model

Background Chronic Fatigue Syndrome (CFS) is a complex and poorly understood illness that affects between 1 and 4 million individuals [1,2] and costs an estimated $35 bil lion per year in lost productivity and health care [3,4]. Persistent and unexplained fatigue has been observed as a sequela of acute infection since the first half of the 20th century and the period’s notable outbreaks of infec tious disease (e.g., polio epidemics, influenza pan demics). From 1934 to 1984, there were several reports of infectious disease outbreaks simulating poliomyelitis [5,6] though no causal pathogen was isolated from the majority of the cases. Clinical investigation of individuals who did not recover several years after initial infec tion showed persistent symptoms of fatigue, sleep

* Correspondence: [e-mail] 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 Full list of author information is available at the end of the article

disturbance and cognitive impairment [7,8]. Following an outbreak investigation in 1984 by the Centers for Disease Control and Prevention (CDC) in Incline Village, Nevada [9], an international group of medical experts defined this protracted postinfection illness as chronic fatigue syndrome (CFS) [10]. Since then, post infection illness that lasts for more than six months is a central component of CFS, and studies have shown that the incidence of CFS following infection with a number of different pathogens is about 10% [1114]. The patho gens that most commonly lead to CFS in prospective studies are those that cause infectious mononucleosis (IM)/glandular fever (mainly EpsteinBarr virus (EBV); occasionally cytomegalovirus (CMV), human herpesvirus 6, hepatitis A, and adenovirus [11], Q fever and Ross River virus (mainly in Australia [13]), enteroviruses [15] and parvovirus B19 [16,17]. Indeed in recent work by Kerr and colleagues, antibody testing for EBV, entero virus, Coxiella burnetii (causative agent of Q fever) and

© 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.