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biomolecules: Bioenergetic and Proteomic Profiling of Immune Cells in ME/CFS Patients: An Exploratory Study - Fernandez-Guerra et al - 2021

Discussion in 'BioMedical ME/CFS Research' started by Kalliope, Jun 29, 2021.

  1. Kalliope

    Kalliope Senior Member (Voting Rights)

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    biomolecules: Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study
    Fernandes-Guerra et al

    Abstract
    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease.

    Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction.

    Here, we evaluated patients' symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls.

    We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being.

    This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency.

    They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels.

    Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.
     
    EzzieD, Ravn, inox and 17 others like this.
  2. Londinium

    Londinium Senior Member (Voting Rights)

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    This field is crying out for replication studies and (to my untrained, somewhat uninformed try) this is yet another study finding similar mitochondrial issues. Anyone got a good overview of these studies / seen a good review paper? Would be good to compare results / where in the ATP production process issus have been found / what types of cells were tested.
     
    EzzieD, Chezboo, Ravn and 10 others like this.
  3. glennthefrog

    glennthefrog Established Member

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    time and time again the same results, and nothing ever changes for us... we're still being treated as hypochondriacs and hysterical when some 8000 studies show that our bodies are a complete wreck, specially in regard to energy producing cellular systems . I just don't understand anymore what the point of these studies is, nothing ever, ever changes for us. So tired and frustrated...
     
    Ravn, borko2100, cfsandmore and 4 others like this.
  4. Hutan

    Hutan Moderator Staff Member

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    Small (6 patients) Danish study.
    It's free access - you can download the pdf.

    Paula Fernandez-Guerra
    Ana C. Gonzalez-Ebsen
    Susanne E. Boonen
    Julie Courraud
    Niels Gregersen
    Jesper Mehlsen
    Johan Palmfeldt
    Rikke K. J. Olsen
    Louise Schouborg Brinth

    Aarhus University, Odense University Hospital, University of Southern Denmark, Statens Serum Institute, Rigshospitalet, Nordsjaellands Hospital

    Looks to be nicely written up and minimal BPS overall.

    So, one of the six was just Fukuda compliant - so not clear if they have PEM.


    The Fatigue Scale of Motor and Cognitive function could be worth checking out further.


    Screen Shot 2021-06-30 at 12.36.27 PM.png


    The list of proteins found to be different in this very small sample is interesting:
    Here's a bit explaining coupling efficiency and also explaining that we aren't yet getting overwhelming agreement on what is happening in ME/CFS mitochondria, with different techniques perhaps explaining different findings.
    @DMissa
     
    EzzieD, Ravn, borko2100 and 13 others like this.
  5. strategist

    strategist Senior Member (Voting Rights)

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    A subunit the mitochondrial complex V was also abnormal. That's similar to the complex V inefficiency previously reported.
     
    Marky, Aslaug, Ravn and 6 others like this.
  6. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    The biggest problem with studies like this is the assumption that patterns of glycolysis or mitochondrial respiration in PBMCs is somehow relevant, despite the fact that the microenvironment for PBMCs is quite different to other tissue types.
     
    Jaybee00, Aslaug, Ravn and 8 others like this.
  7. EducateME

    EducateME Established Member

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    Attached Files:

    Ravn and Michelle like this.
  8. borko2100

    borko2100 Senior Member (Voting Rights)

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    Ok so now multiple studies are showing a similar mitochondrial problem. Seems to me like normal energy production is impaired so we rely on backup energy systems (see mtor upregulation). Maybe, due to the inefficiency of those systems and the fact that they are meant to only be auxiliary and thus used sparingly, their overuse (as a result of intense physical / mental stimulation) leads to the production of damaging substances or direct cellular damage resulting in PEM?
     
    Mij, merylg, Mithriel and 1 other person like this.
  9. Ravn

    Ravn Senior Member (Voting Rights)

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    Michelle, Mithriel and Hutan like this.
  10. Aslaug

    Aslaug Moderator Staff Member

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    Michelle, Trish and Andy like this.

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