Cytokine signature associated with disease severity in chronic fatigue syndrome patients

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This shouldn't be a mystery to anyone who follows along with the stuff we discuss on this forum:
"TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway"
http://stke.sciencemag.org/content/9/415/ra19

What I haven't yet looked into though is looking downstream, what are the transcription factors for TGF-Beta and related proteins?..
 

AndyPR

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Is chronic fatigue syndrome real? Life-threatening condition can leave sufferers bed bound

CHRONIC fatigue syndrome - also called "yuppie flu" - affects thousands in the UK. But there's long been debate about whether the symptoms of extreme tiredness and muscle pain are all in the sufferer's mind.
(CFS) - also known as Myalgic Encephalopathy (ME) - is a long-term illness with a wide range of symptoms and no known cause.

It affects 250,000 people in Britain who will suffer from extreme tiredness, muscle pain, sleep disorders, headaches and flu-like symptoms.

A recent study by Stanford University has suggested for the first time that the condition is driven by chronic inflammation.

They also discovered that the condition could soon be diagnosed by a blood test.
http://www.express.co.uk/life-style...uppie-flu-symptoms-treatment-cure-controversy
 

Wonko

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The Express, the Mails dimmer, but slightly less ....., cousin.

Only 6 glaring errors in the snippet posted above, don't think it's worth giving them a click.myself

edit...well I was bored so did click through, the actual article is a bit better but I have to wonder how old some of the bits are- referring to the department of social security which has been the department of work and pensions for years, and years etc.
 
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AndyPR

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Cort's write-up.
There’s nothing like a high-profile study from a major university. For one thing it can get you publication in one of the most prestigious journals around. The journal the Montoya/Mark Davis study was published in, The Proceedings of the National Academy of the Sciences, is the official publication of the National Academy of Sciences. Its website gets about 21 million hits a month; this study is going to get around.

Dr. Jose Montoya, the leader of the Stanford Myalgic Encephalomyelitis/Chronic Fatigue (ME/CFS) Initiative has been talking about this study for years. Now that it’s finally here, it’s making an impact with many media outlets picking it up.

The results were positive and that was good news indeed. This was one study we really didn’t want to fail.
http://simmaronresearch.com/2017/08...igue-syndrome-mecfs-is-inflammatory-disorder/
 

lauluce

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Promising, based on what I've read so far, in common with everything else that seems to have happened today.

Pretty sure it's probably all a dream so looking forward to the cure being released tomorrow.

Come on, PACE debunking, this, in one day......can't be happening
what happened REGARDING pace?
 

lauluce

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AndyPR

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AndyPR

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Nothing new, just another simple article reporting on the paper.
Myalgic encephalomyelitis, or chronic fatigue syndrome, is a condition with unknown causation. In 2017, a group of researchers led by Jose Montoya did a study to determine if there is an immunologic component to the severity and duration of symptoms experienced by patients affected with this condition.
Myalgic encephalomyelitis, or chronic fatigue syndrome, is a condition with unknown cause characterized as having persistent unexplained fatigue of at least six months which impairs activities of daily living.

In an article published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) Journal this 2017, a group of researchers led by Jose Montoya conducted a study to explore the association of different cytokines in the disease severity and duration of myalgic encephalomyelitis. Cytokines are cells secreted by the body’s immune system which can have different effects on other cells. Cytokines from 186 patients diagnosed with myalgic encephalomyelitis and 388 healthy controls were gathered by collecting blood specimens and analyzed using a cytokine assay.
https://www.medicalnewsbulletin.com/immunologic-component-chronic-fatigue-syndrome/
 

nandixon

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If @necessary8 ’s excellent hypothesis of a CD39 deficit of some kind is applicable, then the correlation of severity in ME/CFS with inflammatory cytokines as found by Montoya might correspond to the patients’ genotype with respect to ENTPD1, the gene that codes for CD39.

This is because (mRNA) expression of CD39, at least with respect to Tregs, is primarily genetically driven. In fact, a single tag SNP, rs10748643, determines to a large extent the frequency of CD39+ Tregs that a person produces.

In particular, the GG genotype (which produces more CD39+ Tregs) does a much better job of suppressing inflammatory cytokines than AA:

To answer the question if the AA and GG genotypes differ in their suppressive capacity, we performed suppression assays using total Tregs either from AA or from GG donors and responder cells from the same unrelated donor. We could show that, indeed, AA donors were poor suppressors of IFN-g and IL-17, while even very few Tregs (ratio 0.125:1) from GG donors suppressed 80% of cytokine production (Fig. 5E), thus establishing a direct relationship between genotype and regulatory function. Of note, suppression of proliferation was not significantly different in these donors.

CD39 SNP results.png

Reference: The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation (Full text here.)
 
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FMMM1

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This is a great find @nandixon I would be very interested in seeing if Ron found any alterations to this gene in his severly ill study, as he did full genome sequencing there.
There have been reports of one genetic mutation turning up in all the severely ill patients. I guess it's covered in the Open Medicine Foundation’s Community Symposium, “Molecular Basis of ME/CFS”.
 
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Full free text: Cytokine signature associated with disease severity in chronic fatigue syndrome patients
Note Mark Davis of Stanford is the senior author, and it's PNAS, which is one of the very top journals, which should help generate interest. Well, the media uptake suggests it has, not least the Science New piece (a v well respected and high profile source of news for researchers). More clues link immune system imbalance with chronic fatigue syndrome | Science | AAAS

And just to make my day, they did it properly, correcting for the fact that they made many comparisons (which makes chance associations much more likely). See below:

P values shown are for the significance of the linear trend. Only statistically significant linear trends adjusted for multiple comparisons (P < 0.05) are shown.

View attachment 22764
(from powerpoint slide provided by PNAS so presumably fine to show here).
The cytokine study confirms work by Nancy Klimas and adds support to the theory that there is an Immune dysfunction in ME CFS. There is still the unknown problem...... what causes the dysfunction? is it a virus, is it genetic predisposition, is it a combination of both? We are working on this