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Multi-omics Examination of Q Fever Fatigue Syndrome Identifies Similarities with Chronic Fatigue Syndrome (Preprint, 2020) Raijmakers et al.

Discussion in 'BioMedical ME/CFS Research' started by Michiel Tack, Aug 26, 2020.

  1. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    Abstract:
    Full preprint available at: https://www.researchsquare.com/article/rs-54097/v1
     
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  2. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    This is an interesting comment in the Discussion section:
     
    Last edited: Aug 26, 2020
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  3. spinoza577

    spinoza577 Senior Member (Voting Rights)

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    If I recall rightly,

    the pathogen coxilla burnettii survives - strangely - in the phagosome. Its SOD is, in contrast to other cells, not manganese dependent. A sequestering from Mn, done by the host (Kehl-Fie and Skaar 2009), therefore hasn´t effects on the pathogen´s defence against H2O2 coming from the host (a comparable strategy is seen in S. aureus, Garcia et al 2016).


    I think I got the thought from this article here:

    Coxilla burnettii Superoxide Dismutase Gene: Cloing, Sequencing, and Expression in [E. coli] Heizen et al 1992


    But this one, which I just have found, looks interesting, too:

    Supervision of Monocytes Functions by Coxilla burnettii: Impairent of the Cross- Talk between avb3 Integrin and CR31 Capo et al 1999
     
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  4. Art Vandelay

    Art Vandelay Senior Member (Voting Rights)

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  5. Grigor

    Grigor Senior Member (Voting Rights)

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  6. MeSci

    MeSci Senior Member (Voting Rights)

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    Should 'prole' read 'profile'?
     
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  7. NelliePledge

    NelliePledge Moderator Staff Member

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    So if they’re so similar is there really any point in having something called Qfever fatigue syndrome?
     
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  8. rvallee

    rvallee Senior Member (Voting Rights)

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    For sure I know who's going to lose while these people are jerking each other over imaginary philosophical conundrums: the patients. As usual. It's always the patients who lose.
     
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  9. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    Yes, thanks. Don't know why this was copied wrong from the pdf. Will change it.
     
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  10. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    I thought it was interesting that they highlighted 4E-BP1 as being significantly increased. @DMissa reported the same thing in his Complex V papers quoted below.
     
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  11. MeSci

    MeSci Senior Member (Voting Rights)

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    Could you also change this: "...QFS patients exhibit more of an inflammatory profile that CFS patients..."

    Should be "...than CFS patients..."
     
  12. DMissa

    DMissa Established Member

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    It is interesting. These are, however, related but different measurements. In this thread's paper, from what I can see, the levels of 4E-BP1 in plasma were measured and elevated.

    In our paper, it is the intracellular ratio of phosphorylated 4E-BP1 to total 4E-BP1 reported in the figure which you shared (reflecting elevated TORC1 activity, since the phosphorylated 4E-BP1 is normalised to total 4E-BP1 in the same samples).

    So, two related but separate conclusions.

    In brief, for those who are foggy or find my explanation too wordy regarding 4E-BP1 comparisons:

    The paper here: elevated levels of 4E-BP1 in plasma.

    Our paper: elevated phosphorylation of 4E-BP1 by TORC1 in lymphoblasts (internally accounting for total 4E-BP1 levels).
     
    Last edited: Aug 29, 2020
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  13. butter.

    butter. Senior Member (Voting Rights)

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    Hi,

    thank you for being here!

    Could you give us an update about your next steps and a timescale for these plans?

    Also are you looking for funding?

    Is there any antioxidant that you see could help in the pathology you and your colleagues found?

    Thank you!
     
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  14. DMissa

    DMissa Established Member

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    I will PM you so as not to derail the thread.
     
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  15. Andy

    Andy Committee Member & Outreach

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  16. J.G

    J.G Established Member

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    Interesting. This is a Dutch study. The Netherlands experienced a "Q Fever epidemic" (link) between 2007-2011. Some 20% of patients went on to develop so-called "Q Fever Fatigue Syndrome" (QVS). I took a look at the official government guidelines on QVS (link to document, in Dutch). It describes fatigue as the primary symptom of QVS, in addition to:

    - Unrefreshing sleep (93%)
    - Increase in symptoms following exertion, also known as PEM (93%)
    - Concentration and memory problems (80-87%)
    - Headaches (83%)
    - Muscle pains (73%)
    - Joint pains (63%)
    - Sore throat and/or tender lymph nodes (24-39%)
    - Depression (26%)

    The document even says that where clinical depression is suspected, it should not be considered mutually exclusive with QVS. And yes, the term "PEM" is used, literally and unapologetically. One could seamlessly transplant this paragraph into a text on the clinical presentation of MECFS, and nobody would suspect that it originally described QVS.

    I would comment what a difference it makes to know the original pathogen - but we often do know the precise viral / bacterial trigger in individual cases of MECFS...

    Screenshot attached.
     

    Attached Files:

    Last edited: Nov 29, 2020
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  17. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    I don't have enough concentration to figure out the overall pattern right now (it is complex!).

    Despite only a brief mention in the discussion, the common link of 4EBP1, MMP1, AXIN1 is relationship between cellular adhesions (cell-cell and cell-extracellular matrix interactions) and metabolism through WNT signalling pathways.

    I note the following:

    Axin1 is a negative regulator of WNT signalling pathway
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967064/

    Integrins regulate mmp1/collagen balance during tissue development or repair: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460049/

    Integrin signalling can regulate WNT signalling https://www.nature.com/articles/srep20395

    (from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524117/)
    (note β-catenin and E-cadherin are part of the WNT signalling pathway)

    The WNT pathway is also a key regulator of mTOR, in more ways that mentioned in the discussion of the Q fever study.
    https://en.wikipedia.org/wiki/Wnt_signaling_pathway
    Also side note:
    https://en.wikipedia.org/wiki/TGF_beta_Activation
    (integrins are often involved in TGF-β activation and signal transduction)

    Lastly, I'd like to point out that at least one integrin has been shown to be a key cell entry receptor for Coxiella burnetii
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619019/

    I have previously noted on this forum that integrins are key entry receptors for a variety of viruses including SARS-CoV-2, certain enteroviruses (Coxsackievirus) and certain herpesviruses (such as EBV and CMV). Even when not absolutely necessary for cell entry, there is still a possibility of altered regulation due to surface receptors (or fragments) of the virus or bacteria interacting with these integrins. The question is whether this can induce (or "kindle") long term persistent feedback loops or long-term damage due to dysregulation during the tissue repair process (in the capillary endothelium, or peripheral sensory axons, for example, leading to persistent sensitisation)
     
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