Changes in the transcriptome of circulating immune cells of a NZ cohort with ME/CFS (2019) Sweetman et al

I saw this posted on the "ME/CFS-Evolving Science" facebook page...

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome
Eiren Sweetman, Margaret Ryan, Christina Edgar, Angus MacKay, Rosamund Vallings, Warren Tate (NZ)

International Journal of Immunopathology and Pharmacology Volume: 33 Article first published online: January 11, 2019; Issue published: January 1, 2019

https://doi.org/10.1177/2058738418820402

"Our exploratory approach has enabled us to obtain a rich differentially expressed gene dataset to identify changed biology in ME/CFS. We have identified the circadian rhythm dysregulation pathway as a new possible underlying cause of the unrefreshing sleep, fatigue and metabolic abnormalities seen in ME/CFS. Furthermore, impaired mitochondrial function and resulting oxidative stress, coupled with chronic immune-inflammatory signalling, provides a compelling explanation for the fatigue, cognitive dysfunction and post-exertion malaise experienced in ME/CFS.

Therefore, this study is a further step towards gaining an understanding of the disease process and identifying putative biomarkers to support clinical diagnosis. The biological pathways identified offer a rational explanation of the complex and often multi-systemic nature of ME/CFS."

 

@Keela Too @adambeyoncelowe . Do not let NICE wimp out on sleep hygiene. The problem is that we can't " self-correct" our sleep

 

Full abstract, although link in the original post above gives access to full paper.

 

One of the grant application for NIH center was a sleep related project, although I can't remember what type of study it was.

 

@ScottTriGuy @JaimeS


"The Devil is in the detail "

From the same paper, supplemental material :






Link : https://journals.sagepub.com/doi/su...8820402/suppl_file/Supplementary_Material.pdf

Also mentions on PPAR signaling :

 

I'm not sure there's anything particular about our sleep. It's "unrefreshing" not because of anything in particular, it's just that nothing is. For sure some have disturbed sleep patterns but that may just be coincidence, it's a common problem. When nothing gives you back energy, it's just normal that sleep would fail at that too.

 

In my case, it was part of ME/CFS. I had many issues with my sleep and the amazing thing is that as i was beginning to feel better, so was my sleep getting deeper, i was able to recall dreams (something that hasn't happened for years) and also the duration of the sleep was gradually being increased. At the worst point of my problems i was getting around 4.5-5 hours sleep per day

 

@Alvin

 

Dear Rvallee
Our family member had good normal sleep. Obviously, before an exam there might be anxiety, but sleep was good. Once the ME hit overnight, the sleep also tanked, and tanked so badly meds were required and still it is not good.

 

That' s around what i get without ME with around 2-3 breaks in it. ...I have never been a good sleeper .

 

Thanks for pinging me on this one

I gotta read this when i have cognitive functioning
I'm gonna run it past my sleep neurologist when i see him next

 

It's worth checking out the reference given for the circadian issues. Have only scanned it so far; it's a very long article but looks interesting though not directly addressing ME.

Sounds like there are several different 'clocks' in our body, including in immune cells.

So it's not just about sleep-wake cycles but all sorts of other stuff, too, e.g. inflammation and immune reactions have a circadian rhythm so if something goes wrong there you could end up with a whole lot of issues that have little to do with sleep - but may have a something to answer for in ME.

ETA: The article in question is:
Comas, M, Gordon, CJ, Oliver, BG. (2017) A circadian based inflammatory response – Implications for respiratory disease and treatment. Sleep Science and Practice 1: 18.
https://sleep.biomedcentral.com/articles/10.1186/s41606-017-0019-2

ETA-2:
FWIW, my own sleep is ok-ish at baseline but goes completely haywire in PEM.

 

From the paper:

This is intriguing. Does anyone know what “concepts of Precision Medicine with appropriate statistical analysis” means, exactly? And if it's any good at overcoming the limitations of minute sample sizes (which ME research seems to be full of)?

 

My sleep is desperate since ME started, it was hypersomnia initially, now complete insomnia. I've tried so many meds. I need some kind of horse or elephant tranquilizer. The insomnia started early December and I can't get a handle on it. I crave Orange juice when I wake. It's so messed up.

 

I recently read this book "Why We Sleep" by Matthew Walker who runs sleep lab research. It impressed me because everything was objective, for instance when they did a study about appetite and sleep they weighed all the food people were given and how much they left, no questionnaires!

The most important findings in the book was that sleep is an active, complex process. As a biologist, over the years there have been findings that stunned me and were so obvious it made me wonder why I hadn't realised them before. Even earthworms and molluscs sleep. Something that is so conserved by evolution when it is energy intensive is vital to an organism.

I don't think our sleep is "disturbed" in the trivial sense it is often used but there is a real possibility that the basic neurological functioning of sleep is damaged for us and causing waking symptoms. So many of our biological systems are involved it would be strange if sleep was not. The IOM may have hit on something important by coincidence.

I would love if there was a large scale research project using sleep labs to investigate all aspects of the sleep process in ME.

 

Not sure if it is relevant but I noticed in the supplementary notes that the majority of patients had 'glandular fever' as their onset

This may produce a group with similar characteristics in some ways but I haven't looked to see if there is any research on post-EBV immune signatures

 

I slept like a baby the first 11 years of illness. Then something changed, I started experiencing hypersomnia and then terrible insomnia for a few years, then back to sleeping ok again. I don't have problems sleeping when I have PEM.

Some pwME experience severe insomnia from day one. My dear friend took serious heavy medications to sleep for 18 yrs.

 

Like others, at the beginning of ME I had hypersomnia followed by insomnia to this day caused by a strong wired-but-tired feeling at night.

I also very often get this intense abdominal/gut irritation feeling and itching in my psoriasis areas only during sleep time at night. It will constantly wake me up and cause my brain to suddenly become totally awake and not able to fall back asleep. The intense irritation feels like it travels up my enteric nervous system to my brain and wakes it up while exhausting me at the same time. This symptom will only start after initially falling asleep and goes away by early morning.

The abdominal/gut irritation is like nothing else I’ve ever experienced, it’s a horizontal line of irritation across my abdomen just above the bellybutton. It’s hard to tell what specific part of the gut it’s coming from. It also sometimes feels like I have an upset gut like I ate something wrong, but never results in diarrhea or anything like that.

I know these symptoms are likely are due to overexertion and part of PEM because when I aggressively rest these symptoms go away and only come back once I’ve overexerted again.

I started getting nighttime insomnia for the first time in my life about 1 to 1 1/2 years before getting sudden onset ME. I slept like a baby my entire life before that. I started getting the nightly psoriasis itching symptoms in my early 30s, though I’ve had psoriasis my entire adult life. ME has made it worse and I’m fairly certain there is a connection.

Because of all this, ME has made it nearly impossible to sleep properly and at a normal time. It’s one of the most debilitating and life-ruining parts of my ME. It generally pushes me to sleeping during the day and up at night, so it inverts my sleep cycle.

The symptoms are so powerful that medications that help with sleep don’t work after a while and I would have to increase the dosage. So I stopped using them on a regular basis because the only thing that works to promote regular sleep is to cut exertion.