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Could this be a possibility? (Auto immunity and cortisol)

Discussion in 'Hormones' started by Skippa, Jul 23, 2017.

  1. Skippa

    Skippa Anti-BS

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    Describing this at a very high level, with little development of the possible actual micro events involved, humour me...

    One of my little imaginative pet theories is that the auto-immunity aspect of ME is a reaction to our own cortisol.

    Something... B cells?... is responding to and attacking our own produced cortisol. For some reason. A subsequent macro immune response ensues... "we are under attack".

    Is that even possible?

    Oh, and somewhere along the line, as a result of this, calcium channel uptake is affected negatively too.

    Wild goose chase? Impossible?

    Yes, I know it's a very layman theory, but it seems to fit...
     
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  2. Valentijn

    Valentijn Senior Member

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    Cortisol tends to be too high in the morning and too low in the afternoon/evening, from what I recall? If there was auto-immunity, I'd think it would be more consistently low.
     
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  3. Skippa

    Skippa Anti-BS

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    @Valentijn thanks, I need this to be shot down so that I can stop thinking about it.

    But, immediately, 2 possibilities come to mind:

    1) cortisol triggers the response "help we're under attack" but then isn't adequately dealt with "run for the hills" rather than "fire" - or not enough antigens are produced whatever - using what little reserves we have.

    2) more cortisol is produced as a response to replace the attacked stuff, leading to the snowball effect of PEM continuing to increase AFTER the event, followed by the crash (somewhat akin to the notion of adrenal fatigue). (Wired but tired).

    Hmmm, clutching at straws? Maybe, but is this at least even possible?

    (After-thought - raised cortisol is a RESPONSE to increased stress of all types, but what if cortisol itself ALSO contributes to its own release (cause AND response), thus locking in a cycle of doom (PEM) until one side or the other runs out of resources?)
     
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  4. alex3619

    alex3619 Senior Member

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    There is data that has, I think, still not been published. I think they found we had too much beta cortisol receptor. This creates cortisol resistance. So our actual levels of cortisol that we respond to are much lower. I have been waiting for this to be published for maybe a year now.

    In order to effectively talk about autoimmunity we have to have a candidate receptor, and evidence of antibodies to that receptor.
     
  5. Skippa

    Skippa Anti-BS

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    Hmmm... this kinda supports the flaky notion I have that cortisol plays a role... more cortisol == more trouble.

    (And further down the line explains calcium uptake problems too).

    You mention candidate receptors and antibodies... is it possible (very simply) that nobody knows what that antibody looks like - thus never looking for or finding it?

    Or even a trojan horse effect - it looks totally benign.

    Whatever, I'm waffling now and out of my depth, but feel that when the world's scientific experts liberate us from our imprisonment of a disease, we are gonna be hearing all about the words "cortisol" and "calcium".

    /morning brain flatulence
     
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  6. alex3619

    alex3619 Senior Member

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    That is the issue with antibody research in a nutshell. There are huge numbers of different antibodies in the body. We have to develop tests for each one. Further, different people will have different antibodies with the same function ... antibodies are an adaptive response, not genetically determined. The cells involve actually shuffle their genes around.

    Finding all the possible antibodies is a lot like finding all the needles in all the haystacks in every country in the world.

    Once we know for sure which receptor or other target is attacked it is much easier to focus research on that target, as its typically genetically stable.
     
  7. alex3619

    alex3619 Senior Member

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    Yet we have a lower cortisol response if this is right. Cortisol first stimulates the immune system, then at higher doses calms it. This bivalent response complicates any interpretations.
     
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  8. alex3619

    alex3619 Senior Member

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    In the late eighties I was in a study on a genetic problem with cortisol binding globulin that results in a CFS like syndrome. Issues with cortisol transport are associated with CFS symptoms. I have not gone back to confirm they are associated with ME symptoms. It looks like CBG is a hormone, not just a transport molecule.

    I did not have any of the known genetic issues with CBG.

    All of this is very complicated. I do think cortisol is important though, I just have trouble figuring out the details as the science is not advanced enough, or I just don't know the relevant scientific facts.
     
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  9. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    So a hormone is bound by a hormone?
     
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  10. alex3619

    alex3619 Senior Member

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    CBG is classically considered a transport molecule. However cortisol is easily transported in blood without it. It also has hormone motifs, that is structures we find in hormones. It easily binds with the cell membrane, and has as part of its structure a similar structure found in other hormones that is active inside cells. Its hypothesized its a hormone, and modifies the cortisol response, but I am very out of date on this research. Decades out of date.
     
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  11. A.B.

    A.B. Senior Member

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    There are so many worthwhile lines of research to pursue. The problem is complicated as well: many researchers think that ME/CFS includes several different diseases. We need large studies to get the statistical power necessary to clearly identify subgroups. Until health and funding authorities decide they will solve this problem by making the required funds available, progress will depend more on luck than anything else. I think science has progressed enough to give us worthwhile lines of research, but at this point the problem is mainly political and organizational.
     
  12. alex3619

    alex3619 Senior Member

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    Yep.
     
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  13. Gingergrrl

    Gingergrrl Senior Member

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    @Skippa, in your theory, do you mean that the B cells are creating auto-antibodies that are attacking cortisol or that are attacking cortisol plus all kinds of other things, too? Why cortisol?... And is there an actual autoantibody test for this (am just curious b/c I have no clue)!

    This theory of ME/CFS being a calcium channelopathy really interests me (or else that a calcium channelopathy is a similar but different illness).

    I agree with this as well and once science unravels this, I believe "ME/CFS" is probably hundreds of different yet similar illnesses or sub-groups. I belong to another group where every single person in it has the exact same calcium auto-antibody that I do (which must be a bio-marker of something since it is measurable on a blood test?) and yet we each present with such different triggers, histories, and symptoms. Most are doing IVIG and Rituximab and consider themselves to have an autoimmune illness like me but we are all just as lost as to what it means! Some have cancer, some do not. Some have LEMS, some do not. Some have Myasthenia Gravis, some do not. Some have 10+ different autoantibodies like me. But what does it really mean?!! :bang-head:
     
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  14. alex3619

    alex3619 Senior Member

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    A thousand years from now, medical historians will likely look back and say it was so darn obvious. What can you expect from a primitive society?

    Sigh.

    Science works slowly, and is very bad using old methods at dealing with complexity. Doctors also do not do complexity well. We might find that this changes in time, but its too darn slow for anyone who is already sick.
     
  15. Gingergrrl

    Gingergrrl Senior Member

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    I am hoping it is sooner than a thousand years :eek: although I suspect that you may be right about this!

    Your words made me think of something that my Endo said at my last appt. He monitors my thyroid and cortisol levels, etc, and several of my blood tests were abnormal. I updated him about my IVIG and upcoming Rituximab and how I have all of these auto-antibodies but they do not form a coherent disease with a name and he replied, "Yet". He said at this point in science, I have a bunch of seemingly random auto-antibodies and symptoms but there will be a point in the future that my illness will be known and understood. I found that comforting (even though I doubt it will occur in my life time)!
     
  16. Paralee

    Paralee Senior Member

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    @Skippa . I just read an article (right or wrong) on that. I've been looking for it in my search history for you and can't find it, but it had adrenals (cortisol) with something else, and it mentioned CFS in it. And I don't know if it was a confirmed article with source or just "an article".
    Hopefully I saved it, I'll keep looking, remind me if you don't hear back, if you're interested in it.
     
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  17. Skippa

    Skippa Anti-BS

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    Hi that sounds v interesting, thanks @Paralee

    Eta: ps, sorry @Gingergrrl I haven't ignored you I was writing out a reply but it's gone from my text box now, I'll attempt to explain my reasoning sooooon :)
     
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  18. Gingergrrl

    Gingergrrl Senior Member

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    No worries and I never even thought that! I often get very behind in replying to some threads and PM's and totally understand! Take your time.
     
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  19. Aroa

    Aroa

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    How difficult is it to find the target with the current technology ?

    Given Mark Davis´ findings , is it still relevant the CDR approach to find a treatment ?
     

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