Review: 'Through the Shadowlands’ describes Julie Rehmeyer's ME/CFS Odyssey
I should note at the outset that this review is based on an audio version of the galleys and the epilogue from the finished work. Julie Rehmeyer sent me the final version as a PDF, but for some reason my text to voice software (Kurzweil) had issues with it. I understand that it is...
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ME/CFS and GWI patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase

Discussion in 'Latest ME/CFS Research' started by hixxy, Mar 18, 2017.

  1. hixxy

    hixxy Senior Member

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    J Med Virol. 2017 Mar 17. doi: 10.1002/jmv.24810. [Epub ahead of print]

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Gulf War Illness patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase: Implications in disease pathophysiology.

    Halpin P, Williams MV, Klimas NG, Fletcher MA, Barnes Z, Ariza ME.

    Abstract

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) are debilitating diseases with overlapping symptomology and there are currently no validated tests for definitive diagnosis of either syndrome. While there is evidence supporting the premise that some herpesviruses may act as possible triggers of ME/CFS, the involvement of herpesviruses in the pathophysiology of GWI has not been studied in spite of a higher prevalence of ME/CFS in these patients. We have previously demonstrated that the deoxyuridine triphosphate nucleotidohydrolases (dUTPase) encoded by Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV) possess novel functions in innate and adaptive immunity. The results of this study demonstrate that a significant percentage of patients with ME/CFS (30.91-52.7%) and GWI (29.34%) are simultaneously producing antibodies against multiple human herpesviruses-encoded dUTPases and/or the human dUTPase when compared to controls (17.21%). GWI patients exhibited significantly higher levels of antibodies to the HHV-6 and human dUTPases than controls (p = 0.0053 and p = 0.0036, respectively), while the ME/CFS cohort had higher anti-EBV-dUTPase antibodies than in both GWI patients (p = 0.0008) and controls (p < 0.0001) as well as significantly higher anti-human dUTPase antibodies than in controls (p = 0.0241). These results suggest that screening of patients' sera for the presence of various combinations of anti-dUTPase antibodies could be used as potential biomarkers to help identify/distinguish patients with these syndromes and better direct treatment. This article is protected by copyright. All rights reserved.

    This article is protected by copyright. All rights reserved.

    KEYWORDS:
    Chronic Fatigue Syndrome; Epstein-Barr virus; Human herpesvirus 6; antibodies; deoxyuridine triphosphate nucleotidohydrolase; varicella-zoster virus

    https://www.ncbi.nlm.nih.gov/pubmed/28303641
    http://onlinelibrary.wiley.com/doi/10.1002/jmv.24810/abstract
     
    merylg, wastwater, Woolie and 8 others like this.
  2. Kati

    Kati Patient in training

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    Exciting! We are getting closer.
     
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  3. anciendaze

    anciendaze Senior Member

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    Now, if only we can connect this to research on metabolic abnormalities, we might start to think about prevention and cures.
     
  4. A.B.

    A.B. Senior Member

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    Can you explain how this ties in with other recent research?
     
    Last edited: Mar 19, 2017
  5. M Paine

    M Paine Senior Member

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    Full paper -> http://sci-hub.cc/10.1002/jmv.24810

    More or less, they are suggesting that reactivation of EBV, VZV, or HHV-6A is a result of the immune system failing in CFS/ME and GWI. In addition, that auto-reactive anti-bodies against human dUTPase may contribute to disease in some patients. I can't really see any flaw in that logic, it's nice that they don't attest to this being causative. How much the human dUTPase anti-bodies contribute to disease, who knows.




    I'm not so sure about their model in fig 3... I would have thought "Disruption of Immune Responses" would have included reduced NK cell/T-cell function, but instead they show that as a byproduct of viral cell lysis. Someone correct me if I'm wrong, but reduced NK function is more ubiquitous among patients than co-morbid viral reactivation. Which seems to suggest that it may be more closely tied to the etiology of this disease, rather than a downstream consequence of viral reactivation.

    [​IMG]
     
    Last edited: Mar 19, 2017
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  6. Kati

    Kati Patient in training

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    No, @A.B. sorry I can't. I am no scientist.
     
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  7. A.B.

    A.B. Senior Member

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    No problem, it sounded a bit as if you were seeing a connection.
     
    Last edited: Mar 19, 2017
  8. Kati

    Kati Patient in training

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    Here is my train of thought. DR Klimas and a few others like Peterson, Kogelnik and Montoya have known for a while now about the implication of herpes viruses in the pathogenesis/pathology of ME. Here, they are providing novel mechanisms.

    I have no doubts that it ties in with other groups' latest research. Dr Klimas will speak at Invest in ME this year and can't wait to hear what she will have to say.

    So like I said, I cannot tie in scientifically, it is out of my scientific limits.
     
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  9. RogerBlack

    RogerBlack Senior Member

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    Are they?
    I only skimmed the abstract, but surely the same result would happen if you got an auto-antibody generated against the virus (or other causative or auto-antigen triggering agent) at the time of infection, and then that is entirely causing all of the pathology going forward.
    Stress (of whatever form) causes the auto-antibody to flare.
     
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  10. M Paine

    M Paine Senior Member

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    I just noticed that they used Optical Density as their measurement of antibody titres from their ELISA screening. This is really not enough to determine the quantity of antibody in these samples.
     
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  11. hixxy

    hixxy Senior Member

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    Klimas is an immunologist no?
     
  12. M Paine

    M Paine Senior Member

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    Yes, but the lead author(s) seem to be out of a different lab. I wouldn't be suprised if she, or any other reviewers may have pointed out the limitations of using OD for quantitative analysis.
     
  13. M Paine

    M Paine Senior Member

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    Only 7 out of 55 ME patients screened positive for human dUTPase reactive antibody. 7 out of 151 controls also screened positive.

    They observed no evidence of molecular mimicry:

    The paper is suggestive of some other breakdown in immune regulation allowing for viral reactivation, and increased incidence of auto-reactivity.


    Have a full read yourself, I'd be interested to hear what you come away from this paper with.
     
    Last edited: Mar 19, 2017
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  14. ash0787

    ash0787 Senior Member

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    I had a bad viral flare up a few days ago which made me feel like I was going to pass out, nausea etc,
    it passed fairly quickly but it was clear to me that in the following days the immune system was overactive,
    I noticed changes to the area of my finger which usually indicates a sort of auto immune attack and originally coincided with a deterioration of function level. Since then I have felt extra tired and especially rough in the morning, I tend to struggle a lot more with viruses like colds etc than I used to, I usually have to reduce activity level for about a week after. I do worry that one of these times its going to cause a more longer term recalibration of the immune system which will make the disease worse.
     
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  15. AndyPR

    AndyPR Senior Member

    Article - https://hhv-6foundation.org/cogniti...ential-biomarker-for-gulf-war-illness-and-cfs
     
    M Paine likes this.

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