Immunologic Mechanisms, Biomarkers and Subsets in Chronic Fatigue Syndrome (CFS)

Summary

Principal Investigator: MARY A FLETCHER
Abstract: Chronic Fatigue Syndrome (CFS) is an illness that has been estimated to affect 800,000 people in the United States. Up to 80% of those affected are women. These individuals suffer from severe fatigue that impairs daily activity, diminishes quality of life for years and has no known cure. CFS represents an economic burden for society and its healthcare institutions. Hypothetical initiating events for CFS include infections, psychiatric trauma and exposure to toxins. An emerging body of evidence demonstrates alterations in the immune system. Immunologic impairment may lead to episodic activation of latent viruses -held in check in healthy individuals by cytotoxic lymphocytes. Current treatments for the syndrome are symptom-focused and relatively ineffective. Improved treatment options will come with a better understanding of the underlying pathophysiology of the syndrome. Our goal is to improve the understanding of CFS pathophysiology and to develop biomarkers useful in diagnosis, in defining subsets and in therapeutic trials. The rationale for the proposed research is based on our work and that of others that suggests immune dysfunction in CFS. In this study, we will use a longitudinal study design that incorporates, within an 18-month window, two random time points and two time points corresponding to the patient perception of times of relative intensification and relative amelioration of CFS related symptoms. We have two Specific Aims. Specific Aim 1 will determine the extent to which patients, or subset of patients who meet the CFS case definition have immune impairment, or patterns of immune dysfunction, as compared to healthy, sedentary controls. Specific Aim 1 will determine the relationship of immune markers related to lymphocyte cytotoxic function, lymphocyte activation and inflammation to symptom severity over the 18 months of observation. Specific Aim 2 will define the molecular biology of impaired immune function in CFS on samples collected at the four time points and allow us to determine if changes in disease severity correlate with changes in the lytic pathway of cellular immunity. By defining immune function at the molecular level, we will identify potential biomarkers and targets for intervention with immuno-modulatory therapies and the means to measure the efficacy of these therapies.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome
    MARY A FLETCHER
    Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL USA
    Behav Brain Funct 6:76. 2010
  2. ncbi Biomarkers for chronic fatigue
    Nancy G Klimas
    Miami Veterans Affairs Medical Center, Miami, FL, USA
    Brain Behav Immun 26:1202-10. 2012
  3. ncbi Exploring the diagnostic potential of immune biomarker coexpression in Gulf War Illness
    Gordon Broderick
    Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Edmonton, AB, Canada
    Methods Mol Biol 934:145-64. 2012
  4. ncbi Psychoneuroimmunology and natural killer cells: the chromium release whole blood assay
    Mary Ann Fletcher
    Department of Medicine, University of Miami, Miami, FL, USA
    Methods Mol Biol 934:313-24. 2012
  5. pmc Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue
    Gordon Broderick
    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
    J Transl Med 10:191. 2012
  6. pmc Plasma cytokines in women with chronic fatigue syndrome
    Mary Ann Fletcher
    Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL, USA
    J Transl Med 7:96. 2009
  7. pmc A formal analysis of cytokine networks in chronic fatigue syndrome
    Gordon Broderick
    Division of Pulmonary Medicine, Department of Medicine, University of Alberta, College Plaza, 8215 112 Street NW, Edmonton, Alberta, Canada
    Brain Behav Immun 24:1209-17. 2010
  8. pmc Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26
    MARY A FLETCHER
    Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
    PLoS ONE 5:e10817. 2010

Scientific Experts

Detail Information

Publications8

  1. pmc Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome
    MARY A FLETCHER
    Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL USA
    Behav Brain Funct 6:76. 2010
    ..Abnormalities in stress responses have been identified as potential triggers or mediators of CFS symptoms. This study focused on the stress mediator neuropeptide Y (NPY). We hypothesized that NPY would be a useful biomarker for CFS...
  2. ncbi Biomarkers for chronic fatigue
    Nancy G Klimas
    Miami Veterans Affairs Medical Center, Miami, FL, USA
    Brain Behav Immun 26:1202-10. 2012
    ..Until such a molecular signature is obtained efforts to develop effective treatments will continue to be severely limited...
  3. ncbi Exploring the diagnostic potential of immune biomarker coexpression in Gulf War Illness
    Gordon Broderick
    Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Edmonton, AB, Canada
    Methods Mol Biol 934:145-64. 2012
    ..In a separate test set these same features allowed for discrimination of new GWI subjects (n = 16) from unhealthy (n = 9) and healthy control subjects with a sensitivity of 70% and a specificity of 90%...
  4. ncbi Psychoneuroimmunology and natural killer cells: the chromium release whole blood assay
    Mary Ann Fletcher
    Department of Medicine, University of Miami, Miami, FL, USA
    Methods Mol Biol 934:313-24. 2012
    ..Target cells are the K562 eyrthroleukemia cell line. Killing capacity is defined as number of target cells killed per effector cell, at an effector cell/target cell ratio of 1:1 during a 4 h in vitro assay...
  5. pmc Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue
    Gordon Broderick
    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
    J Transl Med 10:191. 2012
    ..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...
  6. pmc Plasma cytokines in women with chronic fatigue syndrome
    Mary Ann Fletcher
    Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL, USA
    J Transl Med 7:96. 2009
    ..No widely accepted laboratory test or marker is available for the diagnosis or prognosis of CFS. This study screened plasma factors to identify circulating biomarkers associated with CFS...
  7. pmc A formal analysis of cytokine networks in chronic fatigue syndrome
    Gordon Broderick
    Division of Pulmonary Medicine, Department of Medicine, University of Alberta, College Plaza, 8215 112 Street NW, Edmonton, Alberta, Canada
    Brain Behav Immun 24:1209-17. 2010
    ..Furthermore this analysis identifies key sub-networks such as IL-2:IFN-γ:TNF-α that might be targeted in restoring normal immune function...
  8. pmc Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26
    MARY A FLETCHER
    Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
    PLoS ONE 5:e10817. 2010
    ..However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS...