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

Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome
Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome
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.
Abbreviations: CFS, chronic fatigue syndrome; NBS, National Blood Service; PBMC, peripheral blood mononuclear cells; PCR, polymerase chain reaction.
chronic fatigue syndrome, pathogenesis, gene expression, T cell activation, mitochondrion, neurone, organophosphate, virus infection, interleukin 10 receptor
0021-9746
826-832
Kaushik, N.
e483c946-968f-49d7-80ad-04485e30dc07
Fear, D.
1f474ee5-7ca9-41f6-9ba2-b65a05dca51c
Richards, S.C.
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McDermott, C.R.
9e69f9f9-387c-4fe7-813a-4167cd7283dd
Nuwaysir, E.F.
ec63c5fc-9f6d-41cc-a3e8-5074249ab3b1
Kellam, P.
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Harrison, T.J.
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Wilkinson, R.J.
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Tyrrell, D.A.
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Holgate, S.T.
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Kerr, J.R.
6ec5ede4-c23e-4f97-9e6f-4273c1cfd5c7
Kaushik, N.
e483c946-968f-49d7-80ad-04485e30dc07
Fear, D.
1f474ee5-7ca9-41f6-9ba2-b65a05dca51c
Richards, S.C.
a7a48a2d-78a1-4418-8f1d-442dee9fd5bc
McDermott, C.R.
9e69f9f9-387c-4fe7-813a-4167cd7283dd
Nuwaysir, E.F.
ec63c5fc-9f6d-41cc-a3e8-5074249ab3b1
Kellam, P.
d7d08551-d66d-4a9e-8839-35c028e66f81
Harrison, T.J.
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Wilkinson, R.J.
d08be0b9-dbe4-46c5-9297-68733a4e2f9f
Tyrrell, D.A.
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Holgate, S.T.
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Kerr, J.R.
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Kaushik, N., Fear, D., Richards, S.C., McDermott, C.R., Nuwaysir, E.F., Kellam, P., Harrison, T.J., Wilkinson, R.J., Tyrrell, D.A., Holgate, S.T. and Kerr, J.R. (2005) Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. Journal of Clinical Pathology, 58 (8), 826-832. (doi:10.1136/jcp.2005.025718).

Record type: Article

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.
Abbreviations: CFS, chronic fatigue syndrome; NBS, National Blood Service; PBMC, peripheral blood mononuclear cells; PCR, polymerase chain reaction.

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More information

Published date: 2005
Keywords: chronic fatigue syndrome, pathogenesis, gene expression, T cell activation, mitochondrion, neurone, organophosphate, virus infection, interleukin 10 receptor

Identifiers

Local EPrints ID: 27197
URI: http://eprints.soton.ac.uk/id/eprint/27197
ISSN: 0021-9746
PURE UUID: 217c454e-33f4-41f9-8ec1-8b0b863db074

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Date deposited: 26 Apr 2006
Last modified: 15 Mar 2024 07:16

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Contributors

Author: N. Kaushik
Author: D. Fear
Author: S.C. Richards
Author: C.R. McDermott
Author: E.F. Nuwaysir
Author: P. Kellam
Author: T.J. Harrison
Author: R.J. Wilkinson
Author: D.A. Tyrrell
Author: S.T. Holgate
Author: J.R. Kerr

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