RESEARCH - Abnormal gene profile found in chronic fatigue patients

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Abnormal gene profile found in chronic fatigue patients

Rheumawire

August 12, 2005

Janis

London, UK - Patients with chronic fatigue syndrome (CFS) have abnormalities

in gene expression, and these changes carry intriguing hints about factors

that might trigger or contribute to this syndrome, according to Dr

R Kerr (now at St 's University of London, UK). Kerr and colleagues at

Imperial College, London, report in two papers in the August 2005 issue of

the Journal of Clinical Pathology that they have identified a reproducible

gene-expression profile in peripheral blood monocytes from CFS patients [1]

and that CFS may be associated with the HLA-DQA1*01 allele [2].

" Historically, CFS has been relatively unexplained in terms of biological

function. This pilot study was designed to test the hypothesis that

abnormalities of gene regulation occur in CFS, and we have shown that to be

the case, " Kerr tells rheumawire. " We have now taken this a step further and

identified the very pathways involved, and that will be described in our

next paper. The fact that we have found reproducible changes in gene

function in CFS supports the view that this disease has a biological or

organic basis and is not just in the mind. "

Genes suggest T-cell, neuron, and mitochondrial changes

In the first paper, the researchers describe a characteristic

gene-expression profile in CFS patients, which includes upregulation of 15

genes and downregulation of one gene compared with normal controls. They

also note that the specific genes involved suggest T-cell activation,

neuronal abnormalities, and mitochondrial-function abnormalities.

This study was done using 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. The analysis used a single color microarray representing 9522

human genes, and genes showing differential expression were further analyzed

using TaqMan real-time polymerase chain reaction in fresh samples.

Among the genes upregulated were those for neuropathy target esterase (NTE)

and eukaryotic translation initiation factor 4G1 (EIF4G1). " These genes are

the targets for organophosphates and viruses, respectively, " Kerr says.

" Therefore, we hypothesize that upregulation of each may reflect a host

response to an insult, which attempts to overcompensate in each case. "

The upregulated genes could be grouped according to immune, neuronal,

mitochondrial, and other functions relevant to CFS. The gene-expression

profile suggested T-cell activation, upregulation of protein kinase C family

members implicated in various psychiatric and affective disorders,

abnormalities of microtubule proteins in neurons, and changes in several

aspects of mitochondrial function.

Kerr predicts that these findings will eventually improve the care of CFS

patients by identifying those metabolic pathways that are abnormal in CFS,

leading to development of drugs to bring these processes back to normal. He

tells rheumawire that his group is about to begin clinical trials using

experimental drugs chosen on the basis of the CSF gene-expression findings.

The second paper identifies an association with HLA-DQA1*01 in many CFS

patients, but Kerr says that this is not a not a promising drug target and

that this line of work will not be taken further unless the HLA region is

highlighted in future gene-expression studies. He adds, " We were surprised

that we did not find an association with the HLA-DRB1 locus, as this was

suggested by previous work in CFS. "

Sources

1. Kaushik N, Fear D, s SCM, et al. Gene expression in

peripheral blood mononuclear cells from patients with chronic fatigue

syndrome. J Clin Pathol 2005; 58:826-832.

2. J, Fritz EL, Kerr JR, et al. Association of chronic

fatigue syndrome with human leukocyte antigen class II alleles. J Clin

Pathol 2005; 58:860-863.

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