Utility of the Blood for Gene Expression Profiling and Biomarker Discovery in Chronic Fatigue Syndrome

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.

Identification of Marker Genes for Differential Diagnosis of Chronic Fatigue Syndrome

“…The microarray or differential display approach has been used to examine the CFS-specific gene expression in peripheral blood mononuclear cells (2)(3)(4)(5). Two sources are commonly used for preparation of RNA, whole blood, or its leukocyte populations (15).…”

“…Takuya Saiki, 1 Tomoko Kawai, 2 Kyoko Morita, 2 Masayuki Ohta, 3 Toshiro Saito, 3 Kazuhito Rokutan, 2 and Nobutaro Ban 1 fact, CFS is accompanied frequently by psychiatric disorders such as mood disorders, and the clinical manifestations of these two conditions partly overlap. Therefore, it is important that physicians are able to make the differential diagnosis between CFS and mood disorders, particularly major depression.…”

“…Several groups have been searching for reliable biomarkers for diagnosing CFS and have shown altered gene expression profiles in peripheral blood leukocyte populations, which can distinguish the majority of CFS cases (2)(3)(4)(5). Recently, a data-intensive analysis has been conducted successfully by the Wichita CFS project (6).…”

Gene Expression in Chronic Fatigue Syndrome

“…IL-8 is a proinflammatory chemokine gene with chemotactic properties for neutrophils during pathogen invasion and other immunological insults (Huber et al, 1991). In CFS IL-8 has been shown to be significantly increased in expression in comparison to non-CFS individuals (Vernon et al, 2002). During neutrophil pathogen lysis, phagocytic products are released which acts as a positive feedback process to activate IL-8 to recruit more neutrophils (Ito et al, 2004;Sparkman and Boggaram, 2004).…”

Is multidimensional scaling suitable for mapping the input respiratory impedance in subjects and patients?

“…For large data sets, dimension reduction can effectively overcome the information retrieval complexity. Thus, MDS techniques are used in many applications of data mining and gene network research [30,31].…”