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

Discussion in 'ME/CFS research' started by RoseE, Jan 16, 2019.

  1. RoseE

    RoseE Senior Member (Voting Rights)

    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

    "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."
    boolybooly, inox, Nellie and 17 others like this.
  2. obeat

    obeat Senior Member (Voting Rights)

    @Keela Too @adambeyoncelowe . Do not let NICE wimp out on sleep hygiene. The problem is that we can't " self-correct" our sleep
    Snow Leopard, inox, Nellie and 15 others like this.
  3. Andy

    Andy Committee Member

    Hampshire, UK
    Full abstract, although link in the original post above gives access to full paper.
    inox, RoseE, Ravn and 8 others like this.
  4. obeat

    obeat Senior Member (Voting Rights)

    One of the grant application for NIH center was a sleep related project, although I can't remember what type of study it was.
    merylg, Trish and andypants like this.
  5. mariovitali

    mariovitali Senior Member (Voting Rights)

    @ScottTriGuy @JaimeS

    "The Devil is in the detail "

    From the same paper, supplemental material :


    Link :

    Also mentions on PPAR signaling :

    inox, merylg, Amw66 and 5 others like this.
  6. rvallee

    rvallee Senior Member (Voting Rights)

    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.
    Chezboo, oldtimer, merylg and 5 others like this.
  7. mariovitali

    mariovitali Senior Member (Voting Rights)

    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
    rvallee, pteropus, merylg and 3 others like this.
  8. ScottTriGuy

    ScottTriGuy Senior Member (Voting Rights)

    Alvin and andypants like this.
  9. Perrier

    Perrier Senior Member (Voting Rights)

    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.
  10. Amw66

    Amw66 Senior Member (Voting Rights)

    That' s around what i get without ME with around 2-3 breaks in it. ...I have never been a good sleeper .
    merylg and mariovitali like this.
  11. Hutan

    Hutan Moderator Staff Member

    Aotearoa New Zealand
    It's good to see this study; it feels as though it could contain some clues.

    I need to read it again, and then a few more times, and even then I won't understand everything.

    In the meantime, I do wonder about the graph:

    Screen Shot 2019-01-17 at 11.57.12 AM.png

    (note the numbers on the y axis. Ct value: smaller numbers indicate fewer PCR amplification cycles required to produce enough gene transcript to exceed a baseline threshold. So smaller numbers indicate that there is more of the relevant RNA.)

    The distribution of data points doesn't look that different in PwME and controls - there's a lot of overlap. These are small samples. It would be interesting to know if the people with high levels of IL8 gene transcripts are also the ones with high gene transcripts for NFKBIA and TNFAIP3, and, if so, if there was anything different about those PwME from the significant number of PwME who had levels comparable with the controls.

    Edit: also there don't seem to be 10 data points for each [transcript type+cohort]. Why is that?

    Also this:
    The authors seem to be suggesting a possible causal relationship between disruption of the circadian rhythm and ME/CFS. My son's sleep cycle is definitely delayed. But then, he is also a teenager, with friends that he often plays computer games with who live in a later time zone, and he usually doesn't need to get up early. Efforts to normalise his sleep pattern didn't change the illness.

    I pretty much always wake up at the same time each morning, relatively early. My circadian rhythm is stable and normal unless I have been awake in the night with pain, which is not often. My son and I have similar symptoms. My personal experience doesn't support a direct causal relationship between delayed sleep and ME/CFS symptoms. I'd be concerned if this study was used to support the idea that more advice needs to be given to people with ME on sleep hygiene.
    Last edited: Jan 17, 2019
  12. NelliePledge

    NelliePledge Moderator Staff Member

    UK West Midlands
    As a mild/moderate person my pain level isn’t so high it’s that keeping me from getting to sleep. I consider I have delayed sleep pattern as part of PEM. At the start of PEM it is tired but wired then subsequent nights it goes to delayed sleep - doesn’t matter what time i get up or go to bed. Melatonin helps bring it forward to earlier in the night. Insomnia/sleep timing being out of whack is one of the symptoms I’ve had for a good few years before diagnosis. I somehow used to push through on no or a couple of hours sleep then crash out at weekends. I did ask for a referral for a sleep study but was told only for sleep apnea.......
    merylg, leokitten, Trish and 2 others like this.
  13. Alvin

    Alvin Senior Member (Voting Rights)

    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 :)
    Amw66, ScottTriGuy and andypants like this.
  14. Ravn

    Ravn Senior Member (Voting Rights)

    Aotearoa New Zealand
    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.

    FWIW, my own sleep is ok-ish at baseline but goes completely haywire in PEM.
    Last edited: Jan 17, 2019
  15. Ravn

    Ravn Senior Member (Voting Rights)

    Aotearoa New Zealand
    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)?
  16. Sunshine3

    Sunshine3 Senior Member (Voting Rights)

    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.
    merylg, leokitten, Perrier and 3 others like this.
  17. Mithriel

    Mithriel Senior Member (Voting Rights)

    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.
    inox, merylg, Hutan and 8 others like this.
  18. ukxmrv

    ukxmrv Senior Member (Voting Rights)

    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
    inox, Simon M and andypants like this.
  19. Mij

    Mij Senior Member (Voting Rights)

    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.
    andypants likes this.
  20. leokitten

    leokitten Senior Member (Voting Rights)

    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.
    Last edited: Jan 18, 2019
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