Behan WMH , Gow JW , Simpson K , Behan PO , Chaudhuri A  and McKay IC 
Departments of Pathology , Neurology  and Immunology ,
University of Glasgow
Professor WMH Behan,
Department of Pathology,
Glasgow G11 6NT.
Antiviral Pathway Gene Expression Is Not Increased in Chronic Fatigue Syndrome
Patients with CFS have been reported to show activation of two interferon-induced antiviral pathways, the 2,5A synthetase/RNase L and RNA-regulated protein kinase (PKR) with a specific degradation product detectable in 88% of patients compared to 28% of healthy controls. It was suggested that CFS was due to a viral infection. Patients with documented viral illnesses, however, were not included in the studies. Our aim was to see how their results related to the reported activation. We compared 22 patients with CFS to 10 patients with severe gastroenteritis and 21 healthy controls. The mRNA expression of four key genes was evaluated in peripheral blood mononuclear cells using a standard reverse transcriptase polymerase chain reaction (RT-PCR) technique.
The ratio of mRNA of the antiviral pathway genes compared to that of abl (a housekeeping gene) was calculated. Each ratio for gene expression was tested for differences among the three groups by applying three two-sample t-tests to each possible pair of groups, based on the logarithmic data and the pooled variance of the three. Patients with infection had activation of both pathways: gene expression for PKR was increased, equivalent to a factor of 9.6 compared to healthy controls, and that for the inhibitor RLI was higher by a factor of 17 compared to the two other groups. In contrast, there was no evidence of any significant difference, for any of the genes, between patients with CFS and healthy controls.
Previous results were based on comparison with patients with non-specific syndromes but minor upregulation may persist for 2-3 months after a viral illness. When a group of patients with acute infections is included, it is plain that the changes in the CFS group are not significant. Analysis of antiviral pathway activation therefore cannot form the basis of a rational test for CFS.
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