Abnormal gene profile found in chronic fatigue patients

Janis Kelly

August 12, 2005

August 12, 2005

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 Jonathan R Kerr (now at St George'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 ].

T he 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.

"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 rheuma wire . "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.

This group is about to begin clinical trials using experimental drugs chosen on the basis of the CSF gene-expression findings.

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 rheuma wire that his group is about to begin clinical trials using experimental drugs chosen on the basis of theCSF 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, Richards SCM, et al. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. J Clin Pathol 2005; 58:826-832.

  2. Smith 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.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....