Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome.

Suzanne D Vernon,Irina M Dimulescu,Elizabeth R Unger,William C Reeves,Mangalathu Rajeevan

doi:10.1155/2002/892374

Abstract

Chronic fatigue syndrome (CFS) is a debilitating illness lacking consistent anatomic lesions and eluding conventional laboratory diagnosis. Demonstration of the utility of the blood for gene expression profiling and biomarker discovery would have implications into the pathophysiology of CFS. The objective of this study was to determine if gene expression profiles of peripheral blood mononuclear cells (PMBCs) could distinguish between subjects with CFS and healthy controls. Total RNA from PBMCs of five CFS cases and seventeen controls was labeled and hybridized to 1764 genes on filter arrays. Gene intensity values were analyzed by various classification algorithms and nonparametric statistical methods. The classification algorithms grouped the majority of the CFS cases together, and distinguished them from the healthy controls. Eight genes were differentially expressed in both an age-matched case-control analysis and when comparing all CFS cases to all controls. Several of the diffrentially expressed genes are associated with immunologic functions (e.g., CMRF35 antigen, IL-8, HD protein) and implicate immune dysfunction in the pathophysiology of CFS. These results successfully demonstrate the utility of the blood for gene expression profiling to distinguish subjects with CFS from healthy controls and for identifying genes that could serve as CFS biomarkers.

Highlights

Chronic fatigue syndrome (CFS) is an illness characterized by debilitating fatigue, impaired concentration and memory, sleep disturbances, and pain [8] and it affects approximately 500 per 100,000 adults in the United States [15]
We used hierarchical clustering and multidimensional scaling to determine if the PBMC expression profiles of the CFS cases were distinguishable from healthy controls
One branch contained four (80%) of five CFS cases and five healthy controls

Summary

Introduction

Chronic fatigue syndrome (CFS) is an illness characterized by debilitating fatigue, impaired concentration and memory, sleep disturbances, and pain [8] and it affects approximately 500 per 100,000 adults in the United States [15]. CFS presents a unique challenge for health care providers, public health officials, and patients because the diagnosis is based on self-reported symptoms and requires exclusion of medical or psychiatric diseases that could potentially explain the illness. Once all other medically explainable illnesses have. One reason that CFS remains an enigma to both medical and research communities is lack of a known or accessible anatomic lesion. We hypothesized that peripheral blood would serve as a representative sample of the systemic state allowing for evaluation and profiling of multiple pathologic and physiologic pathways. Peripheral blood is an easy and noninvasive sample to collect.

Objectives

Methods

Results

Conclusion