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 differentially 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.

 

Source: Vernon SD, Unger ER, Dimulescu IM, Rajeevan M, Reeves WC. Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome. Dis Markers. 2002;18(4):193-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851413/ (Full article)

 

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects

Abstract:

BACKGROUND: The association of an infectious agent with chronic fatigue syndrome (CFS) has been difficult and is further complicated by the lack of a known lesion or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection and disease occurring throughout the body. This type of systemic sample coupled with broad-range amplification of bacterial sequences was used to determine whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS and 55 non-fatigued subjects was assessed to determine plasma DNA concentration and the presence of bacterial 16S ribosomal DNA (rDNA) sequences.

RESULTS: DNA was isolated from 81 (91%) of 89 plasma samples. The 55 non-fatigued subjects had higher plasma DNA concentrations than those with CFS (average 151 versus 91 ng) and more CFS subjects (6/34, 18%) had no detectable plasma DNA than non-fatigued subjects (2/55, 4%), but these differences were not significant. Bacterial sequences were detected in 23 (26%) of 89. Only 4 (14%) CFS subjects had 16S rDNA sequences amplified from plasma compared with 17 (32%) of the non-fatigued (P = 0.03). All but 1 of the 23 16S rDNA amplicon-positive subjects had five or more unique sequences present.

CONCLUSIONS: CFS subjects had slightly lower concentrations or no detectable plasma DNA than non-fatigued subjects. There was a diverse array of 16S rDNA sequences in plasma DNA from both CFS and non-fatigued subjects. There were no unique, previously uncharacterized or predominant 16S rDNA sequences in either CFS or non-fatigued subjects.

 

Source: Vernon SD, Shukla SK, Conradt J, Unger ER, Reeves WC. Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. BMC Microbiol. 2002 Dec 23;2:39. Epub 2002 Dec 23. http://www.ncbi.nlm.nih.gov/pubmed/12498618