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ME/CFS and gulf war illness patients exhibit increased humoral responses to herpesviruses-encoded dUTP, 2017, Halpin, Klimas, Fletcher, Ariza et al

Discussion in 'ME/CFS research' started by Hutan, Feb 19, 2021.

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  1. Hutan

    Hutan Moderator Staff Member

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    Myalgic encephalomyelitis/chronic fatigue syndrome and gulf war illness patients exhibit increased humoral responses to the herpesviruses-encoded dUTPase: Implications in disease pathophysiology

    Peter Halpin 1, Marshall Vance Williams 1 2, Nancy G Klimas 3 4, Mary Ann Fletcher 3 4, Zachary Barnes 3 5, Maria Eugenia Ariza 1 2

    https://pubmed.ncbi.nlm.nih.gov/28303641/


    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.
     
    Hutan, Feb 19, 2021
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  2. Forbin

    Forbin Senior Member (Voting Rights)

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    Forbin, Feb 19, 2021
    #2
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  3. Esther12

    Esther12 Senior Member (Voting Rights)

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    I wonder if, even if this holds up, it could just be something associated with ill health generally?
     
    Esther12, Feb 19, 2021
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  4. boolybooly

    boolybooly Senior Member (Voting Rights)

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    I think this anti-vDUTP response is a marker for HHV activity, which is indicative of a subtype of ME CFIDS, of the particular type I have, where the adaptive immune system has been compromised and the innate immune system is highly activated resulting in ongoing viral replication and excessive inflammatory responses including the poorly characterised innate responses which cause the main ME symptoms.

    I think this is useful for confirming diagnosis of just one subtype because I think there are probably other ways the innate immune system can become chronically activated and other dynamics to those ways which may not include HHV proliferation which consitute other subtypes of ME.

    We just dont know. On the one hand I am very glad that someone is looking seriously at EBV + other HHVs as a scenario but on the other hand I dont think this particular observation relates to a causal mechanism, I think is just symptomatic of a bigger problem.
     
    boolybooly, Feb 20, 2021
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  5. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

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    EDIT: I thought this was a new paper but it's from 2017!

    The authors of this paper are NIH-funded researchers who have focused their research on deoxyuridine triphosphate nucleotidohydrolases (dUTPase) encoded by herpesviruses such as Epstein -Barr virus (EBV), human herpesvirus -6 (HHV -6), and varicella -zoster virus (VZV).

    In this study, they looked at the anti - dUTPase antibody response of 58 patients with Gulf War Illness (GWI), 55 ME/CFS patients and 151 controls. The authors report 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%)."

    THe most interesting finding to me is shown in figure 2.D. It shows higher anti-EBV dUTPase antibodies in the ME/CFS cohort compared to the GWI cohort (p = 0.0008).

    upload_2021-2-20_13-49-35.png
     
    Last edited: Feb 20, 2021
    ME/CFS Skeptic, Feb 20, 2021
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  6. Hutan

    Hutan Moderator Staff Member

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    Thanks Michiel. Those four graphs aren't very convincing, are they? There might be statistically significant differences, but there's so much overlap, that it's difficult to believe that levels of dUTPase antibodies are, on their own, the answer to the question of ME/CFS or GWI.
     
    Last edited: Feb 22, 2021
    Hutan, Feb 22, 2021
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  7. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I agree. In terms of being relevant to disease causation those graphs show unequivocally the the differences in antibody levels are not relevant. When antibodies are important the differences stick out like a sore thumb. The fact that they have very commendably given scatter plots makes it all the clearer.
     
    Jonathan Edwards, Feb 22, 2021
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  8. Hutan

    Hutan Moderator Staff Member

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    Hutan, Feb 23, 2021
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  9. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Bupesh Prusty's work comes to mind when you mention dUTPases - but I've no idea if that is relevant to this conversation
    https://pubmed.ncbi.nlm.nih.gov/32327453/
     
    FMMM1, Feb 23, 2021
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    Kitty likes this.

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