Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome

Abstract

Background:Chronic fatigue syndrome (CFS) is a multisystem disease, the pathogenesis of which remains undetermined.Aims:To test the hypothesis that there are reproducible abnormalities of gene expression in patients with CFS compared with normal healthy persons.Methods:To gain further insight into the pathogenesis of this disease, gene expression was analysed in peripheral blood mononuclear cells from 25 patients with CFS diagnosed according to the Centers for Disease Control criteria and 25 normal blood donors matched for age, sex, and geographical location, using a single colour microarray representing 9522 human genes. After normalisation, average difference values for each gene were compared between test and control groups using a cutoff fold difference of expression ⩾ 1.5 and a p value of 0.001. Genes showing differential expression were further analysed using Taqman real time polymerase chain reaction (PCR) in fresh samples.Results:Analysis of microarray data revealed differential expression of 35 genes. Real time PCR confirmed differential expression in the same direction as array results for 16 of these genes, 15 of which were upregulated (ABCD4, PRKCL1, MRPL23, CD2BP2, GSN, NTE, POLR2G, PEX16, EIF2B4, EIF4G1, ANAPC11, PDCD2, KHSRP, BRMS1, and GABARAPL1) and one of which was downregulated (IL-10RA). This profile suggests T cell activation and perturbation of neuronal and mitochondrial function. Upregulation of neuropathy target esterase and eukaryotic translation initiation factor 4G1 may suggest links with organophosphate exposure and virus infection, respectively.Conclusion:These results suggest that patients with CFS have reproducible alterations in gene regulation.

Antibody to parvovirus B19 nonstructural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalomyelitis

“…Restrictions imposed by the NBS on those allowed to donate blood are outlined elsewhere (Kaushik et al, 2005).…”

“…QPCR (Applied Biosystems) was used to quantify the amount of mRNA for the CFS/MEassociated human genes NHLH1 and GABPA by the comparative method, using custom 384-well low-density arrays and the ABI PRISM 7900HT instrument (Applied Biosystems), with GAPDH (encoding glyceraldehyde-3-phosphate dehydrogenase) as the endogenous control gene. Experiments were performed in triplicate using the protocol described previously (Kaushik et al, 2005;Kerr et al, 2008). Data were displayed using SDS 2.2 software (ABI), discordant data between replicates omitted, and results calculated.…”

GABARAPL1 (GEC1): Original or copycat?

“…92 GABARAPL1 is the only member of the GABARAP family that has been shown to interact with the autosomal recessive hypercholesterolemia protein 93 in the brain. Lastly, GABARAPL1 interacts with the starch binding domain-containing protein 1, a protein thought to play a role in glycogen metabolism ( Table 1).…”

Chronic Immune Response Hypothesis for Chronic Fatigue Syndrome: Experimental Results and Literature Overview

“…The results published differ significantly between research groups [Kaushik N et al, 2005;Fang H et al, 2006;Carmel L et al, 2006;Frampton D et al, 2011]. For example, upregulated expression of ABCD4, PRKCL1, MRPL23, CD2BP2, GSN, NTE, POLR2G, PEX16, EIF2B4, EIF4G1, ANAPC11, PDCD2, KHSRP, BRMS1, and GABARAPL1 was found by Kaushik N et al [2005].…”