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New paper by Morris: Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis

Discussion in 'Latest ME/CFS Research' started by Mel9, Oct 16, 2016.

  1. Mel9

    Mel9 Senior Member

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    This new paper by Morris, Berk, Walder and Maes seems to be an excellent comprehensive review of how viruses, bacteria and fungi might be causing inflammation, and thus ME CFS.

    The biochemistry is beyond me but Figure 1 seems to sum it all up.

    In the past few years I have often wondered - 'why do some people with these infections become chronically ill, whereas others do not?' The paper talks about the genetics of ME CFS (see quote below) --how many of us have had the TLR or cytokine genes tested?

    "The role of functional polymorphisms in TLR or cytokine genes in the genesis and maintenance of such a presentation appears to be a promising avenue for research given that such genetic abnormalities are known to influence an individual’s susceptibility to infection, the severity and duration of the immune response, and the development of chronic illness.."
     

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  2. J.G

    J.G

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    Writing review papers seems to be Morris & Maes' jam. They've done a bunch on oxidative stress (here, here) and one on self-perpetuating inflammatory pathways as well. All do a great job of collating disparate findings and applying a macro-theoretical perspective to them. Glad to see they're extending their concern with the aetiology of inflammation in ME/CFS.
     
    Last edited: Oct 17, 2016
  3. trishrhymes

    trishrhymes Senior Member

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    Thanks for the link, @Mel9. This looks really interesting, though mostly beyond me scientifically. I've copied the abstract here for anyone who wants a taster and broken it up to make it easier to read.

    One thing I notice and approve right from the start - they call it 'Intractable fatigue accompanied by cognitive and physical disability - a great way of avoiding the controversy of what to call ME/CFS, and they question the umbrella use of CFS. I guess the only down side of not putting ME or CFS in the title is it might not come up in literature searches, and readers have to infer what they are talking about.

    'The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

    Gerwyn Morris1 & Michael Berk2,3 & Ken Walder4 & Michael Maes2,5
    Received: 24 December 2014 /Accepted: 28 May 2015 /Published online: 17 June 2015 # Springer Science+Business Media New York 2015

    Abstract Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge.

    The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation.

    Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms.

    More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure.

    Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased.

    The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection.

    A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge.

    Examination of lymphoid tissue or CSF in such circumstances may be warranted. '
     
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  4. RogerBlack

    RogerBlack Senior Member

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    I note the above definition fails to include PEM as defining.
    At the very least, this would seem to be an important subset of patients to study, and not splitting those off is approaching as bad as the oxford definition.
     
  5. Valentijn

    Valentijn The Diabolic Logic

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    They're doing a review of the research, and not selecting patients themselves. And they're clearly looking at "intractable fatigue", with ME/CFS as one diagnosis out of many.

    That said, only quacks use Oxford, and quacks don't do quality immunological studies. So I seriously doubt any Oxford studies are impacting their review.
     
  6. trishrhymes

    trishrhymes Senior Member

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    @RogerBlack
    In an earlier study by Maes et al flagged up by @J.G they show they do understand the difference between properly defined ME and fatigue as described in the method below.


    In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.
    Maes M1, Ringel K, Kubera M, Anderson G, Morris G, Galecki P, Geffard M.
    Author information

    Abstract
    BACKGROUND:
    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation.

    METHODS:
    We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale).

    RESULTS:
    The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise.

    DISCUSSION:
    The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder.
    https://www.ncbi.nlm.nih.gov/pubmed/23664637
     
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  7. RogerBlack

    RogerBlack Senior Member

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    Gotta love that p-value.
    Makes the psych studies look kinda pathetic.
     
  8. eljefe19

    eljefe19

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    @Hip check it out, hip, evidence of autoimmune activity against serotonin (causing the neurological symptoms of anxiety/depression?) and evidence that ME/CFS is a neuroimmune disorder.
     
  9. J.G

    J.G

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    One caveat I would place here is that Loebel et al 2016 searched for serum 5HT antibodies in their German and Norwegian ME cohorts, and found no difference between patients and controls.

    In one of their oxidative stress papers, Morris & Maes theorise that modification of biological compounds by ROS could spark immunogenicity. If I understand it correctly, this means that the body would start to identify these 'oxatidative and nitrosative stress modified epitopes', to use their terminology, as foreign, and begin to mount an immune response against them. They call this a secondary autoimmune response. I have no idea if secondary autoimmunity is an established concept in medicine; I'm just parroting what I read.

    Either way, I think we have sufficient evidence of immune abnormalities in ME/CFS to see that oxidative stress is not the sole culprit in ME pathology. That said, it could perhaps be a perpetuating factor in chronic immune activation.
     
    Last edited: Oct 17, 2016
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  10. lansbergen

    lansbergen Senior Member

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    I think the problems start when the early immune response superoxide keeps going on. I only recently found superoxide is an early immune response that can destroy protein and DNA. A molecule which can do that soon after infection is a great tool but it should not go on and on.
     
  11. J.G

    J.G

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    Yes. To my understanding, macrophages release O2 as part of a pathogen-killing respiratory burst. This is a normal aspect of the innate immune response. Of course, tell-tale upregulation of pro-inflammatory cytokines indicate a continuous 'full alert' in early stage ME. The question is why this is happening.

    Macrophages may be producing the O2 that damages proteins, DNA, and so on, perhaps bringing on secondary autoimmunity, but something else presides over the proliferation of those macrophages. Why does that something else think we need them in large numbers?
     
    Last edited: Oct 18, 2016
  12. lansbergen

    lansbergen Senior Member

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    Because the infection I suspect can not be eliminated easy. The experts claimed it could not be destroyed at all.

    I thought my system did not produce enough interferon gamma. I think it does now and that accelerate the healing proces.
     
  13. J.G

    J.G

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    That's certainly one possibility among many. I was posing the question rhetorically though. If we knew the answer with certainty, we'd be much closer to curing MECFS than we are now.
     
  14. lansbergen

    lansbergen Senior Member

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    Yep.

    I am as sure as one can be without a test. I learned more from the healing proces than from the deterioration proces.
     
  15. flybro

    flybro Senior Member

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    G.Morris, I trust him, he's both brilliant and passionate.
     
    Last edited: Oct 19, 2016
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  16. J.G

    J.G

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    Really? How and why did that happen? Sounds like a great loss to the community.

    Yes, I really like the outputs of Morris and Maes. Prolific, top notch (in my layman judgement) and unafraid to push the envelope a little.
     
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  17. eastcoast12

    eastcoast12 Senior Member

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    Lol. BPS: we found cfs/me people are crazy. Our study was rigerous and beautiful (p-value 357.2)

    But what about all those bio studies with p-values way less than .5.
    BPS: nothing to see here, move along
     
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  18. flybro

    flybro Senior Member

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    editing post i think i got the wrong forum, so may well be wrong avout the ban too.
     

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