Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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Could CFS/ME be an endothelial autoimmune disease, which triggers the cell danger respon

Discussion in 'General ME/CFS Discussion' started by Empi, Sep 3, 2017.

  1. Empi

    Empi

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    Apologies in advance for my very limited understanding of the principles underlying the below science.

    After recently relapsing following a 15 year remission, I've spent the past few weeks catching up on research and reading about the great work of Dr. Davis, Dr. Naviaux, and Dr. Fluge/Dr. Mella. In doing so, I keep trying to reconcile the idea that there is "something in the serum", which is causing a cell danger response with Fluge and Mella's findings related to likely autoimmunity and endothelial dysfunction.

    My question is could autoimmune endothelial dysfunction be the trigger that leads to the cell danger response? Perhaps endothelial dysfunction results in a lack for oxygen (see Fluge/Mella patent involving Imdur), which triggers the cell danger response and resulting metabolic problems. Further, could "the something in serum" be an intentional signal sent to protect tissue from a endothelial dysfunction induced by a low oxygen state? Assuming this were the case, perhaps PEM represents the body doubling down on the signal in the serum when exercise further reduces oxygen levels.
     
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  2. dreampop

    dreampop Senior Member

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    So, I'm really tired. But recently, there was a thread on auto-immunity without tissue damage, and what kind of target those auto-antigens might target. That's a plausible scenario for CFS. Many years ago I tried to think of an auto-immune disease without auto-antigens at all. Because there's seemingly nothing to be found.

    I had a read a study of those who developed post-mono CFS, who were tested for cytokines within 2 years of being sick: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480896/. One thing that stands out is Il-8 which is remarkable and significantly high.

    Now Il-8 is produced in the endothelium, stored and released in Weibel–Palade bodies. One cool thing is the WP bodies can "remember" after a prolonged insult (infection) and store more IL-8 to rapidly be released.

    Now here's my psuedoscience, and I since don't like my theory, there are a lot of things wrong with it and I don't really understand the immunology of it. What if the WP remembered wrong, what if they remembered a common vasoactive substance as an antigen? Presumably Il-8 would be high all the time, but many cytokine studies haven't shown that to be the case. I guess it could get "exhausted". I never really went anywhere from here because it never made a lot of sense. The idea is that they would keep meeting the normal substance mistaken for an antigen and start some sort of psuedo-immune response that doesn't really go anywhere because the substance isn't actually being targeted, just recognized and triggering a response. Hence no tissue damage. I guess I was presuming somehow the brain, or I guess the mitochondria, would still recognize this process and trigger sickness behavior. That link doesn't exist that I know of, and probably doesn't, which is just one problem. Another being all the problems of constantly triggering the WP bodies.

    Another interesting thing is vasodilation, which seems to make a lot of PWCFS worse, would support this process by allowing molecules to drift closer to the edge of the endothelium. concentration and exercise cause vasodilation, and that could presumably lead to PEM.

    Anyway, it was just an exercise in imagining an "auto-immunity" without auto-antigens. My oxygen levels are good, so I can't see that being a major problem
     
    Last edited: Sep 4, 2017
  3. msf

    msf Senior Member

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    I think they are both downstream effects of the LPS/leaky gut problem. I think there might also be some autoimmunity in a proportion of ME patients, but I think that this also a downstream effect. I guess we will just have to wait and see who is right, though.
     
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  4. Empi

    Empi

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    How would leaky guy explain the effective, but delayed, response to rituximab in many?
     
  5. msf

    msf Senior Member

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    Leaky guy wouldn´t, but then leaky gut might. The gut is most likely affected by the immune changes wrought by Rituximab. As I said, we just to have wait and see who turns out to be right.
     
  6. Murph

    Murph :)

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    I'm inclined to accuse endothelial dysfunction of being the culprit in PEM.

    The endothelium is involved in vasodilation. In a healthy person vasodilation works like this.

    exercise -> increased blood flow -> shear stress on the blood vessel wall -> Nitric oxide signalling -> vasodilation.

    It certainly seems possible that too much or not enough vasodilation is happening in response to the shear stress of exercise, and that causes the endothelium to signal for a broader immune response (CDR). This, to my mind, provides a perfect explanation for PEM. We exercise then we feel sick.

    Vasodilation issues would also explain POTS and the problems we have with heat.

    I don't see endothelium problems as being causal in the chronic part of the condititon, i.e. the ongoing susceptibility to PEM. I'm more inclined to say that autoimmunity or leaky gut is upstream, causing the failure in systems, including the endothelium. (perhaps calcium channel problems are ruining the ability of the endothelium to produce NO? ) rituximab would work on this upstream problem.

    [My other PEM theory is that maybe the problem is reduced nutrients in the blood at the onset of activity, rather than vasodilation. I like that theory because supplementing amino acids has dramatically reduced PEM for me. The mechanism would be similar - a dramatic reduction in nutrients in the blood causes the body to initiate a shutdown. this latter theory fits with the Fluge Mella pyruvate hydrogenase theory. If the body can't use glucose and so uses amino acids, their circulating levels could fall quite quickly.]
     
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  7. duncan

    duncan Senior Member

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    I am not clear why ME/CFS needs to be an endothelial autoimmune disease when it can be explained by one or more endothelial infections.
     
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  8. mhrps

    mhrps

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    My father died from vasculitis, and till the end of his terrible illness he didn't have classic ME symptoms. He was weak but without PEM. Certainly his brain was also involved in earlier stages of the disease. As I see it, ME is some kind of metabolic/mitochondrial dysfunction of the brain.
     
  9. Empi

    Empi

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    My hunch is that, at least for a subset, their response to Rituximab suggests autoimmunity. Also, the thread discussing anecdotal success with Rapamune may also suggest autoimmunity.

    Another thought is that perhaps Rituximab responders have an autoimmune disease, whereas non-responders, which I understand to be primarily the severely ill, have a different disease, which is not an autoimmune disease.
     
  10. Murph

    Murph :)

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    pibee, echobravo and Empi like this.

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