MicroRNAs (miRNAs) are a fascinating potential factor for ME/CFS because they are malleable; i.e they can change over time, and they affect gene expression. That gives them the power to biologically rewrite who we are.
miRNA’s may be affecting the expression of half of our genes.
While they can’t change our underlying DNA template, they can dramatically change how it expresses itself. Some believe they may be turning on/turning off the expression of up to half our genes.
They’re one of nature’s cleverest answers to the need to be biologically nimble. Like neuroplasticity, though, they can be a double-edged sword. The same process which allows us to adapt biologically to change could allow us to get locked into a suboptimal illness state which is difficult to escape. Like any complex program, the opportunity is there for something to go wrong.
A change in the microRNAs we all carry, then, could have caused a shift in gene expression that set off or contributed to ME/CFS and helped keep it in place. Because it is possible to alter miRNA expression, they also present the nice possibility of resetting our systems by returning our miRNA expression back to a healthy state.
We don’t know if an miRNA shift contributed to, or even caused, ME/CFS to occur, but it’s certainly a worthwhile avenue to explore and some studies in the past have had some success.
This Open Medicine Foundation and Sibylla Hesse Foundation-funded study from Montreal, “Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology“, led by Alain Moreau, did something different. The all-Montreal crew believes they’ve found a way to safely induce PEM in the severely ill.
Causing PEM the Massager Way
They used something called an ABR therapeutic massager device, which “exerts pulsatile compressions on the arm” for 90 minutes to produce post-exertional malaise (PEM). The approach has not been validated by studies, but the ME/CFS patients did report that it produced PEM (fatigue, headache, muscle pain, sleep disturbances, flu-like symptoms), while the healthy controls didn’t report any symptoms.
If successful, the massager presents the possibility of providing an exertional challenge to the severely ill, who are unable to withstand the rigors of an exercise challenge.
Plus, the massager device has the notable advantage of being portable – it can easily be brought to a patient’s home. It provides the potential of safely providing exertional challenges to the severely ill – those in whom, in Ron Davis’s words, “the disease burns brightest”. Whether or not an arm massager is a suitable replicate for an exercise challenge – or whether it needs to be – are questions that future studies would need to answer.
Exertion, or stress challenges have become common in ME/CFS studies because putting ME/CFS systems under load provides much more information. That’s not surprising in a disease that’s practically defined by difficulties with exertion.
As time goes on, more and more interesting ways to stress one’s system have been developed. Peter Rowe, for instance, has found that simply moving the limbs of adolescents with ME/CFS in certain ways can produce symptoms. Cognition tests, TILT table tests, plus a multitude of exercise tests (maximal exercise, one and two-day CPET, invasive CPET, and non-maximal CPET) are commonly used. If you want to go molecular, several researchers have used the Seahorse machine to stress test the mitochondria.
Blood was taken before and after the use of the massager device. The participants also answered numerous questionnaires.
Results
The miRNA analysis predicted most of the ME/CFS patients and healthy controls.
The decision to include an exertional challenge worked, as it produced a sterling sensitivity score (it identified 100% of the ME/CFS patients), a good specificity score (75% – it misidentified only a few healthy controls as patients), an excellent overall accuracy (90%), and a superb ROC (receiver operating characteristic) curve score (AUC = 1).
The miRNA expression in the ME/CFS patients – particularly after the exertional challenge – was dramatically different. Eleven microRNAs differentiated the ME/CFS patients from the healthy controls after exercise. It wasn’t just that the miRNAs in the two groups were different – it was clear that exercise affected the miRNAs more in the ME/CFS patients. Seven miRNAs were altered after exercise in the ME/CFS group versus only two in the healthy controls: exercise appeared to have a bigger impact on the ME/CFS group’s gene expression.
Next, the group took what seemed to me, at least, to be a rather daring step – they used quantitative reverse transcription PCR to determine if the miRNA changes they’d found had actually resulted in an increased or decreased gene expression. They were able to replicate changes in the gene expression in 11/17 of the genes they’d identified.
Next, they used something called a “K-means” method, which classified the ME/CFS patients into four distinct groups. The classification system identified one group, in particular, which suggested that miRNA changes the study had picked up were indeed having an impact. This more severely ill group had it all: they experienced higher rates of fatigue, PEM, sleep problems, more disease comorbidities and much lower functionality than the other groups.
Another group, interestingly, which had the worse cognitive scores of any group suggested that more fatigue, PEM, and sleep problems are not necessarily associated with worsened cognitive problems. Likewise, one’s age, sex, body mass index, and illness duration also had no impact on which group one fell into.
The Gist
- MicroRNA (miRNA) are small bits of RNA which turn on or off the expression of genes. They accumulate over time and may during our lifetimes affect half of our genes.
- The question regarding miRNA is whether an alteration in miRNA expression during an infection, say, caused a kind of biological reset.
- This Montreal study used a kind of massager to induce PEM in people with ME/CFS too ill to participate in the exercise stressors typically used in studies.
- The massager appeared to work. Not only did the people with ME/CFS report an increase in symptoms afterwards (while the healthy controls did not), the study was able to use the differences in miRNA found to effectively predict who had ME/CFS and who was healthy.
- The finding suggested that the exertion stressor altered the miRNA in ME/CFS patients much more than it did the healthy controls (which intuitively makes sense), and that exertion in ME/CFS may particularly affect inflammation and the immune system. A possible intriguing link to inflammation of the blood vessels was found.
- The study was also able to use it’s miRNA findings to differentiate four types of ME/CFS including a more severely ill, severely ill group with increased fatigue, PEM, poorer sleep and functioning.
- The studies findings made sense with what we know and could ultimately lead to a diagnostic test.
- Much more work is needed for that and for that we need BIG, well-funded studies. Future long COVID/ME/CFS studies could help with that.
The Montreal miRNAs
So, what did the up and downregulated miRNAs that showed up in ME/CFS do? The authors reported that most (7/11) play a role in immune responses or inflammation and that one was associated with the muscles.
Most have not been associated with ME/CFS before – but three have been – and that was good news.
The hsa-mir-127-3p miRNA has been found before in ME/CFS. Influenza viruses apparently downregulate the expression of this miRNA in order to evade an immune response. This miRNA regulates the expression of a gene linked to IL-10 – a cytokine which has cropped up several times in ME/CFS. It has been associated with fatigue before, its expression increased after exercise, and it was elevated in the cerebral spinal fluid.
Another intriguing miRNA (hsa-miR-150-5p) linked to inflammation was recently also found in be increased after exercise in ME/CFS. The inflammation connection was interesting, as Nancy Klimas’s intensively monitored exercise studies indicate that inflammatory pathways explode into action in ME/CFS patients during exercise.
Other miRNAs found may affect natural killer cells, T-cells, protection against viruses, etc. Perhaps the most interesting, though, is one (hsa-miR-181b-5p) which has poked up in several exercise studies outside of ME/CFS. It’s been proposed to play a role in inflammation of the blood vessels, and as an ‘endurance regulator’.
This study was small but the fact that there was no difference in illness duration between the more severe and less severe cohorts points to a potentially important finding: that illness severity is not a function of duration. It might seem to stand to reason that the longer one is ill the better chance one has of becoming severely ill but this study’s results did not suggest that. It suggested that people either become severely ill with ME/CFS or they don’t.
Creative Community
From Younger’s heat mapping of the brain, to Rahim Esfandyarpour’s nanoneedle, to Visser’s extracranial doppler technique, to the new Uptime Feet on the Floor sensor, to Moreau’s massager the field is blessed with creative researchers. Each new technique presents new possibilities and challenges as well – as each needs to be validated before it’s accepted both inside and outside of this field and that can take a considerable amount of time.
Conclusions
The fact that the miRNA’s found were able to differentiate the people with ME/CFS from the healthy controls was encouraging.
Moreau’s search for a way to get both the severely ill and post-exertional malaise into the same study appeared to work. Not only did the “exercise” impact the miRNAs of the ME/CFS patients more than the healthy controls, but it affected miRNAs associated with the immune system and exertion. Several miRNAs appeared to jive with the inflammation that Nancy Klimas’s intensively monitored exercise studies suggest happens during exercise in ME/CFS.
The findings made sense and that was good news. Several also have popped up in past miRNA studies – more good news.
In general, the omics studies seem to be going well. They tend to provide findings that make sense, given what we know about ME/CFS.
The authors point out that this study”may provide a foundation for the development of a new non-invasive test to diagnose ME/CFS patients.” This study, then, doesn’t provide a new test but it does produce findings which, if validated, could point to a diagnostic test in the future. In the meantime, the study adds to the growing body of knowledge about ME/CFS, and hopefully helps prepare the way for the diagnostics and treatment breakthroughs we all hope will occur.
Those, though, will take much bigger and more expensive studies. That means substantially more funding which could be coming our way in the form of long COVID/ME/CFS studies.
- Coming up – the Open Medicine Foundation’s Big Long COVID Study
This is interesting. Any massage makes me feel so much worse, even a massage chair in a nail salon.
I also wondered how the MiRNA studied relates (if at all) to the MRNA vaccines for Covid.
Add me to the list of people who respond adversely to massage, depending on my condition at the time. This makes me think that there Might be a viral component, as well.
Thank you, Cort.
Add me to the list also – massage always increases pain and fatigue even though it feels great at the time.
This biochemistry is way beyond me but I did wonder about any relation between MiRNA research and the MRNA vaccines.
Yes any type of massage ALWAYS sends me into a huge flareup!!! I had to stop getting them and stop physical therapy for my back because it was making me too sick.
Add me to the fact the massage makes me worse for several days up to one week
Not me. I love firm masssges, I feel better after them.
hi Cort,
can you please tell on how many patiets and healthy ones this study was done? i can not find it in the abstract, maybe i overlooked it.
Thanks
(It’s always a nice surprise to see a comment from you Konijn ?)
that is sweet of you :-), thank you!
Really interested on finding out details regarding ‘Peter Rowe, for instance, has found that simply moving the limbs of adolescents with ME/CFS in certain ways can produce symptoms’. Does anyone have a link this as it could really help with limiting PEM?
Here it is, Elena.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159386
It is really worth reading his para., ‘Biomechanical and physiological considerations with SLR’, where he discusses the consequences of movement involving stretching of the spinal cord and what this leads to. It makes great sense to me as I get terrible OI and other symptoms from bending over and various arm movements. suggesting lack of blood flow and other things I don’t understand.
WOW, now that is interesting. A simple leg raise and hold increased symptoms in ME/CFS people. No wonder true exertion and exercise “gets us”.
Yes I barley ever brush my teeth because just the arm motion of doing that causes a flareup!!! It’s crazy what little things cause such bad symptoms and flareups in our disease!!! Unfortunately I am only able to shower once a month because it makes me soooooo sick for several days!!!
The thyroid gland and adrenal glands control all the body functions which are affected in ME/CFS so it seems obvious that something is affecting the normal function of both glands. Viral infection is the obvious reason. I have been diagnosed viral sub acute thyroiditis 2003 and also had markedly elevated testosterone and other hormones and noradrenaline as my condition worsened in 2014 . To me it seems like an autoimmune response, inflaming tissue in these glands stimulating adrenaline, and other hormones. Viruses are known to hide in these glands in latent form till reactivation. Immune response causes inflammation and eventually autoimmune adrenal insufficiency. The immune system is unable to clear the virus and the battle goes on with constant inflammation and low cortisol.
This does seem to make sense to me. I get PEM from being washed, having a shower, moving downstairs on a chairlift, had to stop using lift as pain with PEM got too bad. I also suffer from sound sensitivity and have noticed that it is things that vibrate that cause me the most problems. Fireworks cause me problems, even a strong vibration from the wind blowing against the house. My body feels as if it has a lot of inflammation, I feel as if I am constantly burning. Would be good if they could use this as a diagnosis for ME/CFS as it seems to be the only illness that has this awful PEM.
There is a Genetic cause to an illness recently found by the NIN/NIAID which causes Vibration issues I do not have this link now but they are testing people for these now it was also Published in a Journal, it is a specific vibration Gene
Also an Ohio Team of Researchers funded by the NIH believe they found a diagnostic blood test marker for ME/CFS they tested this in thousands & all showed this marker it
has to do with Herpes Virus suggesting HHV6 it was posted in Race to Solve ME/CFS at Ohio State College of Medicine MEDICINE.OSU.EDU Marshall Williams PhD & Maria
Ariza PhD called (dUTPASE) they mentioned they hope the test becomes wide spread they also said their findings are enormous
Hi Aidan, Do you have link to this article? I am not able to find it. Thanks
Aiden and Betty,
i couldn’t find it either, but found the following links
a facebook with good links on “Race to solve CFS/ME”
https://m.facebook.com/groups/314293301959189/
this is what came up when i entered researchers’ names in google
https://medicine.osu.edu/news/biomarker-for-chronic-fatigue-syndrome
and work from Ariza on hhv6 and AD
https://www.idsafoundation.org/news/general/2601/
as well as many results showing work they had done work on epstein barr in 2018 and 2019
https://www.clinicaltherapeutics.com/article/S0149-2918(19)30173-0/fulltext
@Betty I Mekdeci
Yikes!
is this it??
found in a different place,
but have not seen an overview like this
MDPI Open Access Journals
zoom_out_map search menu
Journals Biomolecules Volume 11 Issue 2 10.3390/biom11020185
settings
Open AccessFeature PaperReview
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!
by Maria Eugenia Ariza 1,2
1
Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
2
Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
https://www.mdpi.com/2218-273X/11/2/185/htm
Great news, thanks Aiden
It seems Ohio is a hotbed of creative thinkers. Kevin Hackshaw re:test in link below.
https://wexnermedical.osu.edu/mediaroom/pressreleaselisting/blood-test-spots-fibromyalgia
https://www.summitpainalliance.com/blog/researchers-move-closer-to-blood-test-for-fibromyalgia
and news that a company has licensed test— tho it does not seem to be listed as available on their website yet.
https://www.360dx.com/business-news/exagen-ohio-state-innovation-foundation-partners-develop-fibromyalgia-test#.YDFI_aQTHYU
I was the skeptical one when Mayo doctors tried to convince me I had FMS. Had two doctors trying to convince me it was a real illness. I have always felt it is a label put on symptoms. That not being the cause but the result. Maybe they are getting closer to the WHYS.
i am to ill to search, can you please give me a link?
Does anyone else have constant head ringing and a feeling of being poisoned?
I have both of these thing all the time. The more I exert myself the louder the ringing gets.xx
Yes, Dani. Me too and the ringing is beginning to affect my hearing.
Exertion (and other things) can cause issues with mast cell. Mast cell issues cause my ringing in my ears to get very loud. One of my signs of me starting to have an over response is ringing ears.
I also.
I never had constant head ringing, but most definitely have had a feeling of being poisoned. I honestly thought I was dying. This was in 2017 during a severe crash. High doses of the antiviral, valacyclovir, got rid of the poisoning feeling. It took 6-8 weeks on this drug before noticing improvement.
Yes I feel poisoned!!! Especially when I am going through a PEM flareup I feel totally POISONED!!! Also interesting enough I got tested for HHV6 and am positive with high titers, so I totally believe that is true!
It is always, in the future, perhaps useful as a diagnostic test, if it is validated. Usually on groups of patients that are too small. I fear that we will never experience a scientific breakthrough this century 🙂
Agreed. While this is very intetesting, without large scale testing and substantial funding , it will not lead to actual treatment options any time soon.
Interesting blog Cort, as usual :-). I know very few of this yet. So, that means time to search and learn.
Looking up that 181b mRNA thing, I landed on “Homo sapiens (human) hsa-miR-181b-5p” of rnacentral.org.
It has 25 references to associated research papers and two of them caught my eye. I must they were in line with my suspision of what might induce the PEM. I must admit however that I did cherry pick those papers that sort of are in line with that suspision.
The suspision I started from:
* A repeating compression on the arm, if strong enough and resembling an arm clam for blood pressure measurments enough, recurrently partly cuts of blood flow in that arm.
* Reduced blood flow, if provoked by this device, certainly will have most obvious effects on the affected arm.
* When blood flow is already borderline poor (with ME patients), some repetitive increased blocking of it in the arm can get it borderline unsufficient or trigger some form of increased local hypoxia. Recurrent local hypoxia is part of Issie’s and my ideas regarding to ME.
* When blood flow in the arm is reduced, blood flow towards the arm will be reduced too. Tha
Somehow send too soon.
…
* When blood flow in the arm is reduced, blood flow towards the arm will be reduced too. That should have some modest impact on heart blood volume output. When it’s already low, that again can push it a bit deeper. My expectations would be reduced stroke volume combined with a modest increase in heart rate.
* When blood flow from the heart is impacted, blood flow to much of the remainder of the body will be impacted too including heart prefill.
The two papers on rnacentral.org for that mRNA that caught my eye? I am removing the link to not get blocked by WordPress’ spam filter; they can easily be found on the rnacentral.org webpage.
“Altered Expression of Umbilical Cord Blood Levels of miR-181b and Its Downstream Target mUCH-L1 in Infants with Moderate and Severe Neonatal Hypoxic-Ischaemic Encephalopathy. by A. M. Looney, M. P. O’Sullivan, C. E. Ahearne, M. Finder, U. Felderhoff-Mueser, G. B. Boylan, B. Hallberg & Deirdre M. Murray”
“Association between MEG3/miR-181b polymorphisms and risk of ischemic stroke. by Xuemei Han, Zhaoshi Zheng, Chunhui Wang & Libo Wang”
Ischemia and hypoxia. If that is what happens here it feels like those mRNA are upregulated to try and restore / alleviate a problem, not “trying” to create a bad vicious circle.
I had told Dejurgen about this last night, after I read the blog. He wanted me to tell it here. My experience with arm compression. Having POTS, and Mayo Clinic being a diagnostic place and them trying to not only diagnose you, but make sure no stone is unturned……here was an attempt of a test…….
They wanted to do a 24 hour blood pressure cuff on me to see what my blood pressure and heart rate were doing. It would go off every so many minutes for 24 hours. She put it on me and it started going off. Me being so sensitive to pain and with EDS, it was very painful. It did it about 5 times and I could hardly stand it. I told her I didn’t think I could do it, it hurt too bad. She watched me grimace each time. She said you can’t do this. There is no way and it will probably bruise you really bad. She shut it off and tried to call the doctor. She couldn’t get him. And told me she was making an executive decision and that test was off the table. I knew I couldn’t stand it. And so did she. Was glad she made the call. So with me, it would activate the sympathetic nervous system and wear me out. And bruise my arm and make it very sore.
And, the idea of decreased blood flow to that arm and heart rate issues…. explains a lot, I think. It would had been a miserable 24 hours and would had lasted for way longer than the test did. I could feel a ramp up of my autonomic nervous system, with what it was doing to me with just 5 continuous blow ups of that cuff. Wouldn’t surprise me at all to have PEM from that experience.
GLAD WE DIDN’T DO THAT ONE!
I’ve also had chemical induced stress test. That will create PEM too.
Cort, this is really interesting. I need to reread it again. But in case you don’t answer this question in the blog, would such a diagnostic test have to provoke PEM in order to be diagnostic of ME/CFS? It would be so good if a test could be developed that wouldn’t make us feel worse.
PS To Issie – that 24 hour bp test sounds like a nightmare. Whenever someone ones to use that automatic bp machine to take my bp, I ask if they can’t do it the old fashioned way instead. Even experiencing it once is painful and upsetting.
I was thinking how could this possibly give any accurate indication of what my body “normally” does, if each time it blew up and hurt so bad and my heart rate went up because of pain. Just seemed not so good of a way to do that. Now that the smart watches can check heart rate, maybe some would be able to check blood pressure. Now THAT would be a more accurate test for blood pressure and heart rate, if it could be recorded for 24 hours.
If my gut feeling is right and the effect shows on heart rate (and more so on heart rate variability), then measuring and analyzing that for a while might be fairly accurate as well.
Thank you Cort for article and for saying where it is at now…..
not a test, but …….”may provide a foundation ….”
Any thoughts on where do the microRNA reside? are they present in serum or plasma?
and where do they come from that they:
“They accumulate over time”
Does inflammation or infection cause more of them?
LOL, maybe they are a follow up article in themselves.
Great work as always Cort.
I find it interesting how these passive manoeuvres can induce PEM. Similar with Rowes sham leg raise study where there is no active effort. They seem to go against the theory of insufficient energy creation – in mitochondria- or using up all energy reserves
Rowe speculates that the stretching of the spinal cord in us brings about a number of reactions which also involve loss of blood flow. See his para., ‘Biomechanical and physiological considerations with SLR’
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159386
This was in Cort blog above: “IL-10 – a cytokine which has cropped up several times in ME/CFS. It has been associated with fatigue before, its expression increased after exercise, and it was elevated in the cerebral spinal fluid.”
We can look up IL10 snps. I looked mine up and I had a lot of yellow and red markers on them. (I’m a member of Selfdecode, and my gene testing is from 23&me. He has a whole lot connected there and talks about IL10 being elevated in FMS and ME/CFS. There is supplement advice on how to up expression or down regulate it too. ) If anyone else has access to that, it would be interesting to see how many of us have wonky genes connected to IL10 and IL6. I have issues on both. Both can contribute to inflammation and autoimmune issues.
I wanted to know why possibly IL10 is elevated in ME/CFS. Usually having higher IL10 is a more desired thing than not. Having either too high or too low levels can give issues with different illnesses. Homeostasis is the desired thing with this one. But I found a referenced paper (from the Selfdecode site) that shows that certain virus produces something similar to IL10 in order to evade the immune system and not be attacked. Guess which virus can do this…..EBV, for one. Here is the link. But keep in mind, not all of us test positive for EBV. (Doesn’t mean we haven’t had it, just antibodies are not detected, with our wonky immune systems. BUT, could also mean we have ME/CFS for other reasons than EBV.)
https://journals.plos.org/plospathogens/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002704
An EXCELLANT blog was just posted by Debbie Moon on her Geneticlifehacks blog site. Here is the link:
https://www.geneticlifehacks.com/genetics-chronic-fatigue-syndrome-and-long-haul-viruses/
There are genes that can be checked that can indicate if possibly some of us are genetically predisposed to ME/CFS. (I’m wonky on many of the genes listed here ) She also addresses how virus can affect gene expression and cause us to have epigenetic changes. Also has some more information, about what I posted here, about EBV and it using a similar substance like IL10 to do a sort of “fake out” that it is there to evade the immune system.
Very well done Debbie. Thanks for allowing me to link it here! And thanks for writing it and helping us draw more awareness to ME/CFS and other connected illnesses like POTS.
I strongly recommend reading this study. It is open access. This will be the best study you read on the epidemiology of ME this year. Its a hard read but worthy of the study.
Changes in DNA methylation proiles of myalgic encephalomyelitis/chronic fatigue syndrome patients relect systemic dysfunctions
AM Helliwell, EC Sweetman, PA Stockwell, CD Edgar, A Chatterjee and Warren P Tate
Clinical Epigenetics Journal of Tanslatinal Medicine) 2020 12:167
https://doi.org/10.1186/s13148-020-00960-z
In short:
Of 349 DMCs (differentially methylated cytosines), 56% were hypo-methylated and 44% hyper-methylated in ME/CFS patients compared with healthy controls.
From the 31 genes in the analysis, the enriched functional pathways associated with hypo-methylation were identified by various combinations of the following five genes: RYR1, GNAS, GNG7, GABRB3 and APBA3, and the single hyper-methylation-associated functional pathway was identified with two hyper-methylated genes: LCK and CIITA
Thanks Ian, that is fascinating.
Some of those pathways is what Dejurgen and I are studying too. We have been experimenting with tweaks and finding some bandaids. We hope to get some blogs out on what we are finding. Its a work in progress. Dejurgen mentioned earlier, we are writing and trying to compile our findings and discoveries.
Gives me a few more genes to look into. The study I was in for families with ME/CFS and Mitrochondria function, with the Drs. Lights in Utah, had me in lowest function of 20% of all in the study. I also have issues in all my Mitrochondria complexes, as to function. I knew of methylation issues too. They compared genes and function in that study too. Compared between family members and the group. Was really enlightening. I got some good info from that one.
Have a detailed look at the study. The genes, with the exception of GNAS, are not really the main issue but the epigenetics and the methylation is going to be the main focus.
GNAS, of course is a major issue because of its involvement in G-protein coupled receptor function.
Also the incidence of Idiopathic Diabetes Insipidus is much more common in me/cfs than normals possibly due to the dysfunction of GNAS affecting adenylate cyclase and resulting low levels of vasopressin. (Some people with me/cfs who have DI have been successfuly (50% of cases) with the synthetic hormone desmopressin. Why the other 50% don’t respond is not known. (perhaps their DI was nephrogenic) An interesting study also reported on Health Rising:
https://www.healthrising.org/blog/2017/02/15/treating-chronic-fatigue-syndrome-mecfs-iacfsme-conference-overviews-part-v/
Yes Ian, I took another look at the link you listed. It is interesting how different things (including illness) can change the expression of genes (epigenetic changes). One wonders if there were already predisposition to that response before hand.
I find some of the papers listed above, showing that EBV can also change the expression and detection of the immune system, fascinating.
In certain illnesses there is more expression of certain cytokines. Like for example COVID and the cytokine storms with it. (One thing to note that T cells are impacted here with a release of mast cell degranulation and more cytokines and histamine. Histamine helps regulate the immune system, and T cells. But an over release/response and we get MCAS.) Dejurgen and I are also working on tweaks for this response and it also moderates cytokines. I have more genetic issues that make my tweaks a bit more complicated. But his response is better than mine. We see very encouraging improvement. (Didn’t help that I got a bad infection recently and then over response of my immune system. And now in a flare. Set me back a bit. But headed back up again.)
I appreciate all the links. A lot of the puzzle pieces come together. Wonderful the advancement of science and the hypothesis that make that possible. First there has to be an idea, and then science can follow and either prove or disprove.
Oh, forgot to comment on treating DI by Dr. Bateman.
I know of several POTS people using that drug and say it helps them. My sister is a patient of Dr. Bateman, in Utah, and I think possibly they tried that with her. The study you linked talked about Dr. Bateman using it for ME/CFS and POTS. So many of us complain that water doesn’t seem to go into the cells properly, no matter how much is drank. And with Osmolality issues. (When osmolality increases, it triggers your body to make antidiuretic hormone (ADH). This hormone tells your kidneys to keep more water inside your blood vessels and your urine becomes more concentrated. When osmolality decreases, your body doesn’t make as much ADH. Your blood and urine become more diluted.)
Some have had benefit with this approach. I think a lot depends on the subsets and symptoms trying to be tweaked.
Would be nice to be able to get to the “cause” and not just tweak symptoms. But if we can’t completely “fix” it…..a nice Purple Bandaid ? will do. As long as we don’t stop compensations. If we support function and not suppress necessary and very needed compensations – even if the symptoms are uncomfortable. May be the lessor of two evils. Body trying to SAVE us.
Article says Berlin study that compares long covid and cfs, found that almost 50% of their long covid patients showed increased IL-8.
(many links in news article)
https://www.thailandmedical.news/news/long-covid-german-study-finds-that-almost-50-percent-of-recovered-mild-covid-19-patients-exhibit-persistent-chronic-fatigue-for-six-months-or-more
Inflammation definitely is a major issue with ME/CFS. As is low cortisol levels because of constant inflammation. Look at symptoms of adrenal insufficiency and most fit pretty good with ME/CFS, also as some have previously replied they have got relief of symptoms with low dose 10mg hydrocortisone. I also had improvement in all symptoms on the same dosage when taken for one month. But the improvement was only temporary and seemed to have a detrimental effect on my immune system and I think made the viral infection load greater. Look up autoimmune Addison disease caused by viral infection. Although not full on Addison disease the theory is that the latent virus hides in the adrenals until reactivation and the immune response damages the adrenals causing inflammation and stimulating hormone production. Also effects other parts of the endocrine system like the thyroid and eventually hypothyroidism. My ultrasound on my thyroid showed multiple nodules, and a CT scan on my adrenal glands showed mildly nodular left adrenal gland. Not only does adrenal insufficiency symptoms fit so does hypothyroidism.
Could it be that having low cortisol levels from constant viral inflammation we are lacking cortisol to energize our cells. Also could low cortisol be affecting our immune cells energy and we have trouble with immune cells not being of sufficient energy quality to clear the virus and stop the inflammation and allow the adrenals to function normally and properly energize our cells.
Absolutely . There is nothing wrong with our adrenals its our brains . We have an ACTH deficiency from a dysfunctioning HP axis . With out the ACTH our adrenals are not being told to function. Why this is continued to be ignored in the 21st century is insane to me . Its been obvious for decades . HP axis dysfunction is the number 1 reason for adrenal issues its not the adrenals its the brain thats the problem .
https://www.youtube.com/watch?v=q1de09ghB4M
Check this out Dennis . Cortisol pumping game changer in the treatment of cortisol deficiency . This is what I am doing to treat my CFS . I went from bedbound to working construction again after 8 months of this treatment . Truly amazing .
RJW Yes you may be right about the HPA there may be inflammation in all three areas as once inflammation is initiated from immune response to infection cortisol levels would initially rise, but with ongoing inflammation cortisol levels would drop giving fatigue and also affect immune cells ability to completely clear the virus from which some struggle for various lengths of time for the immune system cells to restore energy as cortisol levels slowly return for the majority but some are unable to overcome. Not all immune systems are the same, some stronger than others. Mine unfortunately has been repeatedly damaged by doctors prescribing prednisone or corticosteroids with active viral infection. So I am hesitant to use any corticosteroids medications.
For those wanting to do a bit more reading on epigenetics this article is good on the relationship between hypermethylation and disease:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791695/
There is an older article on hypomethylation and disease but I am not sure if it is available online:
DNA hypomethylation and human diseases
Ann S. Wilsona, Barbara E. Powera, Peter L. Molloya,
Biochimica et Biophysica Acta 1775 (2007) 138–162