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. 2024 Jul 4;12(7):491.
doi: 10.3390/toxics12070491.

Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses

Jean-Daniel Masson  1 , Ghidaa Badran  1 , Romain K Gherardi  1   2 , François-Jérôme Authier  1   2 , Guillemette Crépeaux  1   3
Affiliations

Widespread Myalgia and Chronic Fatigue: Phagocytes from Macrophagic Myofasciitis Patients Exposed to Aluminum Oxyhydroxide-Adjuvanted Vaccine Exhibit Specific Inflammatory, Autophagic, and Mitochondrial Responses

Jean-Daniel Masson et al. Toxics. .

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

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Example of observations of Al engulfment into control PBMCs (top panel) and MMF PBMCs (bottom panel) exposed for 4 h to Lumogallion-stained AH: Lumogallion signal in red (left panel), LysoTracker signal in green (central panel), and merged signals (right panel). Scale bars: control—20 µm; MMF—30 µm.
Figure 2
Figure 2
Expression level of LC3-II in differentiated PBMCs exposed for 4 h to several treatments. CQ: chloroquine; Rapa: rapamycin; * indicates statistical difference in Mann–Whitney test; ▲: p < 0.05 compared to vehicle treatment; $: p < 0.05 compared to CQ treatment.
Figure 3
Figure 3
Expression level of Rubicon (upper panel) and Nox2 (lower panel) in differentiated PBMCs exposed for 4 h to several treatments. AH: aluminum oxyhydroxide (Alhydrogel®); V: whole vaccine (EngerixB® 20). * indicates statistical differences in Mann–Whitney test; ▲: p < 0.05 compared to vehicle treatment; $: p < 0.05 compared to CQ treatment; ■: p < 0.05 compared to Rapa treatment; +: p < 0.05 compared to AH treatment.
Figure 4
Figure 4
Level of GROα/CXCL1 in MMF patients’ and controls’ differentiated PBMCs exposed for 4 h to Al-containing treatments. * indicates statistical differences in Mann–Whitney test (**: p < 0.01; ***: p < 0.001); AH: aluminum oxyhydroxide (Alhydrogel®); V: whole vaccine (EngerixB® 20).
Figure 5
Figure 5
Expression level of TNF-α in MMF patients and controls’ differentiated PBMCs exposed for 4 h to Al-containing treatments. * indicates statistical differences in Mann–Whitney test (*: p < 0.05; **: p < 0.01); ▲: p < 0.001 compared to vehicle treatment; $: p < 0.001 compared to AH treatment; AH: aluminum oxyhydroxide (Alhydrogel®); V: whole vaccine (EngerixB® 20).
Figure 6
Figure 6
ATP-related OCR (left panel), maximal OCR (central panel), and SCR (right panel) in MMF patients’ and controls’ differentiated PBMCs exposed for 4 h to Al-containing treatments. ▲: p < 0.05 compared to vehicle treatment from same group; +: p < 0.05 compared to AH treatment; AH: aluminum oxyhydroxide (Alhydrogel®); V: whole vaccine (EngerixB® 20).
Figure 7
Figure 7
Synthetic scheme of healthy immune cell responses to immune stimulation (left) and specificities of immune cells from MMF patients (right). See the Section 4 for details about the represented mechanisms in both situations. “formula image” represents the three main consequences expected of Rubicon overexpression in MMF phagocytic cells.
See this image and copyright information in PMC

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References

    1. Institute of Medicine Committee on the Diagnostic Criteria for ME/CFS . Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. National Academies Press; Washington, DC, USA: 2015. - PubMed
    1. Rasa S., Nora-Krukle Z., Henning N., Eliassen E., Shikova E., Harrer T., Scheibenbogen C., Murovska M., Prusty B.K. European Network on ME/CFS (EUROMENE) Chronic Viral Infections in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) J. Transl. Med. 2018;16:268. doi: 10.1186/s12967-018-1644-y. - DOI - PMC - PubMed
    1. Lerner A.M., Beqaj S.H., Deeter R.G., Fitzgerald J.T. Valacyclovir Treatment in Epstein-Barr Virus Subset Chronic Fatigue Syndrome: Thirty-Six Months Follow-Up. In Vivo. 2007;21:707–713. - PubMed
    1. Dennis A., Wamil M., Alberts J., Oben J., Cuthbertson D.J., Wootton D., Crooks M., Gabbay M., Brady M., Hishmeh L., et al. Multiorgan Impairment in Low-Risk Individuals with Post-COVID-19 Syndrome: A Prospective, Community-Based Study. BMJ Open. 2021;11:e048391. doi: 10.1136/bmjopen-2020-048391. - DOI - PMC - PubMed
    1. Borenstein D. Siliconosis: A Spectrum of Illness. Semin. Arthritis Rheum. 1994;24:1–7. doi: 10.1016/0049-0172(94)90102-3. - DOI - PubMed

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