Gene Expression Subtypes in Patients with CFS/ME, 2008, Kerr, Holgate et al

[Hutan]

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diag- nosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of 2.5. Genes showing differential expres- sion were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymer- ase chain reaction.

Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downreg- ulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reac- tion data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1015.3216&rep=rep1&type=pdf
Open access

 

[Hutan]

An old paper (2008) on differential gene expression that I came across while looking for something else. Does anyone know if the techniques used and results are still considered robust and if the work was replicated?

There are some commonalities in the genes for which there are gene expression data in the recent fibromyalgia study - I have yet to compare them in detail.

I thought this was interesting in the light of the recent Gulf War Illness finding of an increased genetic susceptibility to sarin in people with Gulf War Illness, and wondered if the finding had been followed up:

NTE was upregulated in blood of patients with CFS/ME, both in this study and our pilot study [13]. NTE is the primary site of action of organophosphate (OP) compounds, such as sarin, which cause axonal degenera- tion and paralysis due to inactivation of its serine esterase activ- ity [34]. In the nervous system of adult chickens, OP-modified NTE initiates neurodegeneration. NTE probably regulates neuron-glial interactions during development and possibly also during adult life [35]. Exposure to OPs may trigger CFS/ME [36] and Gulf War illness [37]. Furthermore, the heterogeneity of NTE levels seen in patients with CFS/ME is consistent with a role for OPs in only a subset of patients with CFS/ME.

NTE is neuropathy target esterase.

 

[Suffolkres]

An old paper (2008) on differential gene expression that I came across while looking for something else. Does anyone know if the techniques used and results are still considered robust and if the work was replicated?

There are some commonalities in the genes for which there are gene expression data in the recent fibromyalgia study - I have yet to compare them in detail.

I thought this was interesting in the light of the recent Gulf War Illness finding of an increased genetic susceptibility to sarin in people with Gulf War Illness, and wondered if the finding had been followed up:

NTE is neuropathy target esterase.

You can ask Jonathan himself if you wish? I am in touch with him, have his contact details at Kings Lynn Norfolk.

 

[Ravn]

Exposure to OPs may trigger CFS/ME [36] and Gulf War illness [37]. Furthermore, the heterogeneity of NTE levels seen in patients with CFS/ME is consistent with a role for OPs in only a subset of patients with CFS/ME.

Maybe ME after OP exposure subset isn't ME at all but actually a version of GWI, minus the having to go to war bit?

 

[Trish]

Maybe ME after OP exposure subset isn't ME at all but actually a version of GWI, minus the having to go to war bit?

It would be intersting to look into the future to see whether what is currently defined as ME/CFS, on the basis of symptom based criteria, ends up as:

1. a series of more narrowly defined different conditions with different triggers, genetic predisposition and biomarkers, all under a general group with overlapping patterns of symptoms, but recognised as separate diseases;

Or

2. A single disease with a single biomarker and treatment, with a variety of triggers, genetic and environmental factors influencing the particular pattern of symptoms, severity and prognosis for each individual within that single disease;

Or
3. Some of each or something else.

 

[Simon M]

Gene array approaches are generally seen as suspect. Take a small number of patients and controls, scan a huge number of genes and look for differences. I would be surprised if it replicates.

Single-cell RNA sequencing (scRNA-seq) is a more recent approach that is seen as more reliable for a range of reasons. I think Maureen Hanson's or Ian Lipkin's teams have used this approach (and with larger samples). Previous gene array studies (like the one discussed here) have gone nowhere.

 

[Hutan]

Gene array approaches are generally seen as suspect. Take a small number of patients and controls, scan a huge number of genes and look for differences. I would be surprised if it replicates.

Thanks @Simon M. The recent fibromyalgia study I mentioned above said something very similar that had had me wondering.

Only few studies have investigated miR levels in FMS blood so far. Two studies used serum, whereas one report focused on peripheral blood mononuclear cells (PBMC). Their approaches relied on miRNA microarrays with varying panels, a smaller sample size, and a single set of hybridization conditions, compromising the outcome of these tests