The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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What might remissions mean?

Discussion in 'General ME/CFS Discussion' started by MeSci, Jul 27, 2015.

  1. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    This is not related to anything I am currently experiencing, but I have been pondering on two main issues:

    • Do other chronic illnesses show complete or substantial remissions?
    • What could remissions, whether lasting an hour, a day, a week, a month or several years, tell us about our illness - an illness that has proven so resistant to permanent recovery for most of us?

    I've seen a few threads discussing remission, and there do seem to have been some attempts to make structured analyses of what remissions might mean, but haven't yet found any useful theories or conclusions, but then I haven't spent a lot of time searching. There was a very-promising looking one in 2010, but it seemed to end without resolution, and we have learned quite a lot since then.

    By remission I mean something more than improvement - I mean substantially-increased cognitive and physical function, plus improvement in sleep and mood, and decrease in or disappearance of pain, for those who suffer from these. The improvement must include significantly or completely improved resilience to exertion and other things that usually make things worse. The person should feel near-normal again. There should be no PEM.

    I am going to invite some of our resident scientists/doctors to hopefully contribute some expert ideas and knowledge. @Jonathan Edwards, @charles shepherd, @Butydoc

    Please invite others you can think of.

    Individual experiences will also be useful, including what might have led to remission.
     
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  2. trails

    trails Senior Member

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    This is a great question! I would love to hear an explanation for this that ties into the research (and resultant causation theories) that Doctors Fluge and Mella have conducted.
     
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  3. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Before the experts arrive..

    Some of the big-responders to rtx are back doing what they did in life before ME hit. My take is then that remission in ME means that there arent enough "bad" b-cells around to produce autoantibodies, potentially causing one to get the same level of functioning as before. Only when aborting treatment can one tell if treatment have corrected the immune dysfunction for this subset (recovery), or not (remission).
     
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  4. trails

    trails Senior Member

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    @Marky90 - agreed. However, I would also like to hear how the rtx results might tie into the fact that many of us seem to have symptoms that wax and wane, sometimes for months at a time. Do our bodies produce "bad" b-cells in a cyclic or haphazard manner which could account for this?
     
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  5. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    From my understanding its probably related to the amount of short lived plasma cells that are produced by "bad" b-cells. Exactly why the "bad" b-cells potentially produce more short lived plasma cells after exertion(?) remains to be eludicated.. I`m so not qualified to talk about this, so I`ll send the good question over to @Jonathan Edwards !
     
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  6. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    Good points. But some people have had remissions that are instantaneous, and could not conceivably be due to such a sudden disappearance of B-cells, which have occurred as a result of a drug or supplement. I'm thinking for example of @zzz who experienced remission from a single dose of isosorbide dinitrate (Isordil). Could that indicate subgroups with different types of illness, or an effect in a different place in the chain of causation?
     
  7. A.B.

    A.B. Senior Member

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    One idea is that at least some of the symptoms are a survival strategy with the goal of minimizing energy expenditure. How does the body decide when this strategy should be used? Perhaps when the sum of incoming sickness signals from various parts of the body exceeds a certain threshold. And consequently, the strategy is turned off when the sum of these signals falls below a certain threshold. So small changes in health status could confusingly result in disproportionally large changes in symptoms: the proverbial straw that broke the camel's back, and the opposite of that.

    This doesn't seem too far off what many are describing. This is somewhat similar (maybe identical) to the concept of sickness response.

    It's not the only thing I could imagine having this effect. Some ME specialists believe that an altered microbiome is involved in the pathogenesis of the disease. Now I don't know much about the microbiome but I suspect it's a highly complex system with its own dynamics and evolution over time, and it seems plausible that a long dysfunctional microbiome could eventually regain a sufficiently healthy state.

    It also seems possible that a dysfunctional gut / microbiome could generally be an unstable system that regularly produces symptom shifts and fluctuations. Again I'm not expert, so this is more an intuition / suspicion.

    Fluctuating symptoms and flare ups are part of the picture of many autoimmune diseases. I'm not sure we know why. Some of these fluctuations could give the impression of a remission.

    Some also believe that cyclic flare ups are typical for chronic lyme disease (whatever that is).
     
    Last edited: Jul 27, 2015
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  8. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    Yes - my gut is highly predictive of my ME symptoms. Messed-up gut = poor sleep, weakness, anxiety, etc. Healthy gut = more energy, calmer mood, better sleep, etc.

    EDIT - I had a near-remission for several months when my gut function was unusually good following adoption of a leaky-gut diet and supplements. PEM almost disappeared.
     
  9. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I have read through that zzz-thread, and I am not sure if we can deduce anything from such cases, but I guess the answer would be that it could be both (how clarifying! :p).

    What we do know is that two thirds respond significantly to ritux, i guess the natural way forward is to investigate whether rtx-alike medications can help the others. And if the non-responders then respond, the question must be asked: What qualifies as a subgroup?
     
  10. A.B.

    A.B. Senior Member

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    That is nice to hear. I have also found that that the gut seems to be surprisingly relevant in my condition, but I'm not even close to understanding why.
     
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  11. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    One of the things I want to know is why remissions come to an end. Some treatments work initially very well, but then stop working. It seems as though the body has developed resistance, to a drug or other treatment. Maybe one of our experienced scientists can suggest ways in which resistance could occur in this context, and is there a way to get rid of the resistance? Can we turn it off again? (I have visions of turning us off and on again - it often works with computers :D)
     
  12. Marco

    Marco Grrrrrrr!

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    Good question. I can only talk about my own experience which is a pattern of constant illness which has deteriorated over time but over a period of years I've had, as I've mentioned before, occasional short periods of suddenly for no reason feeling just about 1OO%. Then I go out and do something normal and crash back into illness again.

    The sudden 'remission' suggests to me that there is dysregulation rather than an established pathology and that something has 're-set' but the fact that normal activity then triggers a relapse might suggest the opposite?

    As I said - good question and looking forward to hearing what others think.
     
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  13. geraldt52

    geraldt52 Senior Member

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    Sorry, but I posted the following on the Goldstein protocol thread before realizing that this thread had been started for this purpose. Anyway, here's my post again:
    No lasting benefits is my experience as well...scores of times, to scores of medications/supplements. Intuitively I believe that our bodies/brains have adjusted themselves in defense of some underlying condition. If we try to reset the downstream effects without fixing the underlying condition, our bodies just find another way to readjust in defense. I've come to believe that trying to force these "instant remissions", which are more like momentary cancellations, does more harm than good.
     
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  14. Marco

    Marco Grrrrrrr!

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    Just another little observation. I have severe problems with anxiety, ongoing and at times crippling. I appreciate that this is probably not a universal problem in ME/CFS and may only affect a few and anxiety has always been an problem for me even pre-onset although then it was generally context specific. ME/CFS though seems to have ramped it up to a whole new level.

    Nothing I've tried has touched this except for one occasion. I also tend to have occasional muscle pains which verge on cramp/spasm (had a severe episode of torticollis at one stage) and decided to take a Celebrex (anti-inflammatory) tablet that was in the cupboard. Very soon afterwards the constant anxiety was gone - not just reduced or in the background but completely gone as if it had never been there. The effect lasted for a few hours and I haven't been able to repeat the effect - the Celebrex was 10 plus year old so who knows how fresh tablets would work. Or it could just be a one-off coincidence.

    The thing is there are good reasons to suspect a real effect. Firstly Celebrex is a selective Cox-2 inhibitor and Cox-2 has been linked to anxiety :

    http://www.nature.com/neuro/journal/v16/n9/full/nn.3480.html

    and secondly, elevated Cox-2 is either a downstream or upstream (depending on what you read) factor involved in microglial activation :

    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118372

    and according to the above paper benfotiamine might help?

    As I said, anxiety may be particular problem for me exacerbated by ME/CFS but the common mechanisms may still point to microglial activation.
     
  15. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Absolutely cyclic and haphazard! A very good way to put it.

    I need to be a bit more precise but there is an interesting subplot here. An intriguing aspect of the immune system is that it tends to work a bit like the cockpit of an airliner. Decisions are never given to one cell clone to make. There is always a co-pilot to make sure the pilot has not gone bonkers. Intriguingly, although the lymphocytes in sharks are quite different from ours they also have decisions made by two sorts of cells the way we have decisions made by T and B cells.

    The basic co-pilot system for immune responses is that both B and T cells have to agree that an antigen is an alien. Autoimmunity sets in if the B cells shut the door when the T cells have gone to the loo - or perhaps a better analogy is that they fool the T cells into thinking they are attacking an alien when they are attacking self.

    But even within the B cell system there is a beautifully designed co-pilot requirement. B cells expand by chain reaction when a microbe attacks because the more antibody is made the more the antigen can be passed around to new cells to stimulate more antibody. But the new cells obviously have to pick up the antigen by a different handle if they are being shown it by an antibody from the first cell attached to another handle. That has the interesting effect that a single B cell clone can never stimulate itself to make more antibody beyond a certain point. Once there is enough antibody to stick to all the handles on the antigen that B cell can see it cannot stimulate through further handles.

    Forget worrying if it seems too complicated but the basic outcome is that autoantibody production has to come from at least two and more likely several B cells, each recognising a different handle on the same antigen.

    Now B cell clones are in constant competition with each other and even if fairly successful, tend to die out and be replaced by other clones. So what seems likely to happen in autoimmune disease, and there is quite good evidence from tracking b cell clones in joints for instance, is that the collection of B cell clones causing the trouble is constantly changing. A bit like a tennis club, members come and go. But you always have at least two members to play tennis and even if the members have all changed the game is still tennis (making a certain autoantibody).

    So that's a very long winded explanation for why we should expect autoimmune diseases to wax and wane all the time because the tennis club members are always changing and some are better at tennis than others. And so you get cycles of good and bad tennis and it is all haphazard because B cell generation is a random process!
     
  16. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Thank you for an amazing explanation and analogy.
     
  17. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    The gut mucosa are crucial to building and maintaining the immune system, are they not, @Jonathan Edwards? Could this be one key to fluctuations, including full-blown remissions and relapses, at least for some people?

    This looks a rather interesting paper on the gut and immunity.
     
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  18. Sushi

    Sushi Moderation Resource Albuquerque

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    Personal anecdotal experience: After receiving about 20 -30 IV hydrogen peroxide infusions I had a full remission for a couple of years.
    I can only guess that the oxygen from the hydrogen peroxide infusions killed off a good level of pathogens. I didn't know enough to do follow-up and perhaps they multiplied again?
     
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  19. lansbergen

    lansbergen Senior Member

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    Do you mean by that what I call: Tcell failure causes Bcell malfunction?
     
  20. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    No, that is the usual idea that gets taught in immunology but has no real basis as far as I can see. B cells are not the handmaidens of T cells. B cells and T cells are equally in charge. They check things out in different ways. One is the airport attendant that frisks the people who beep on the machine and the other is the sniffer dog. They sense aliens in different ways but they have to agree for the alien to be ejected. In autoimmunity the actual kicking out response is done by B cells with antobody. So if the T cells are suspicious but the B cells are not nothing happens. On the other hand if the B cells are suspicious and they convince the T cells this is an alien by spraying their luggage with a little cocaine then the T cells will start yapping and the B cells can kick them out even if in fact they are perfectly law abiding citizens.
     
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