Widespread Myalgia & Chronic Fatigue:Phagocytes from Macrophagic Myofasciitis...Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit,'24,Masson

Discussion in 'ME/CFS research' started by Dolphin, Jul 7, 2024.

  1. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    5,802
    Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses
    by
    Jean-Daniel Masson
    1,*,
    Ghidaa Badran
    1,
    Romain K. Gherardi
    1,2,
    François-Jérôme Authier
    1,2 and
    Guillemette Crépeaux
    1,3


    1
    Institut National de la Santé Et de la Recherche Médicale, Institut Mondor de Recherche Biomédicale, Université Paris Est Créteil, F-94010 Creteil, France
    2
    Hôpitaux Universitaires Henri Mondor, Service d’Histologie/Centre Expert de Pathologie Neuromusculaire, Assistance Publique-Hôpitaux de Paris, F-94010 Creteil, France
    3
    Ecole Nationale Vétérinaire d’Alfort, Institut Mondor de Recherche Biomédicale, F-94700 Maisons Alfort, France
    *
    Author to whom correspondence should be addressed.
    Toxics 2024, 12(7), 491; https://doi.org/10.3390/toxics12070491
    Submission received: 7 June 2024 / Revised: 29 June 2024 / Accepted: 1 July 2024 / Published: 4 July 2024
    (This article belongs to the Section Exposome Analysis and Risk Assessment)
    Browse Figures


    Abstract

    (1) Background:

    Macrophagic myofasciitis (MMF) is an inflammatory histopathological lesion demonstrating long-term biopersistence of vaccine-derived aluminum adjuvants within muscular phagocytic cells. Affected patients suffer from widespread myalgia and severe fatigue consistent with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood disorder suspected to result from chronic immune stimulation by infectious and inorganic particles.

    (2) Methods:

    In this study we determined the immuno-metabolic properties of MMF phagocytic cells compared to controls, at rest and upon exposure to aluminum oxyhydroxide adjuvant, with or without adsorbed antigens, using protein quantification and an oxygen consumption assay.

    (3) Results:

    MMF and control cells similarly internalized the adjuvant and vaccine but MMF cells specifically expressed Rubicon and Nox2, two molecules unique to the LC3-associated phagocytosis (LAP) machinery, a non-canonical autophagic pathway able to downregulate canonical autophagy. MMF cells exhibited an altered inflammatory secretome, producing more pain-inducing CXC chemokines and less TNF-α than controls, consistent with chronic myalgia and exhaustion of the immune system previously documented in ME/CFS. MMF cells exhibited mitochondrial metabolism dysfunction, with exacerbated reaction to adjuvanted vaccine, contrasting with limited spare respiratory capacity and marked proton leak weakening energy production.

    (4) Conclusions:

    MMF phagocytes seemingly use LAP to handle aluminum oxyhydroxide vaccine particles, secrete pain-inducing molecules, and exhibit exacerbated metabolic reaction to the vaccine with limited capacity to respond to ongoing energetic requests.

    Keywords:
    myalgic encephalomyelitis/chronic fatigue syndrome; macrophagic myofasciitis; aluminum-based adjuvant; autophagy/LC3-associated phagocytosis; inflammation; mitochondrial metabolism

    "The CDC1994 criteria for ME/CFS were fully met in 5/8 patients, this ratio (62.5%) being consistent with the 47–71% range previously reported in MMF [12,40]."
     
  2. DMissa

    DMissa Senior Member (Voting Rights)

    Messages:
    140
    Location:
    Australia
    seahorse data while reporting negative values :emoji_skull:

    You can't have negative spare capacity

    If the basal is higher than the spare capacity it means (either/or):
    1) the basal is already the maximum
    2) the cells are too poisoned by the time the "maximum" is measured to be working well
    3) the uncoupler didn't work

    The most appropriate responses would be to make the spare capacity 0 or preferably repeat the experiment.
     
    Last edited: Jul 8, 2024

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