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Article

Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study

1
Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, 8200 Aarhus, Denmark
2
KMEB, Department of Endocrinology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
3
Department of Clinical Genetics, Odense University Hospital, 5000 Odense, Denmark
4
Section for Clinical Mass Spectrometry, Danish Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institute, 2300 Copenhagen, Denmark
5
Section for Surgical Pathophysiology, Juliane Marie Center, Rigshospitalet, 2100 Copenhagen, Denmark
6
Department of Clinical Physiology and Nuclear Medicine, Nordsjaellands Hospital, 2400 Hilleroed, Denmark
*
Authors to whom correspondence should be addressed.
Both authors contributed equally to the manuscript.
Both authors contributed equally to the manuscript.
Academic Editor: Bhupesh K. Prusty
Biomolecules 2021, 11(7), 961; https://doi.org/10.3390/biom11070961
Received: 21 May 2021 / Revised: 17 June 2021 / Accepted: 18 June 2021 / Published: 29 June 2021
(This article belongs to the Special Issue Biomarkers in Chronic Fatigue Syndrome (ME/CFS))
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. View Full-Text
Keywords: myalgic encephalomyelitis; chronic fatigue syndrome; mitochondria; mitochondrial respiration; spare respiratory capacity; coupling efficiency; pyruvate dehydrogenase; bioenergetics; targeted metabolomics; large-scale discovery proteomics myalgic encephalomyelitis; chronic fatigue syndrome; mitochondria; mitochondrial respiration; spare respiratory capacity; coupling efficiency; pyruvate dehydrogenase; bioenergetics; targeted metabolomics; large-scale discovery proteomics
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MDPI and ACS Style

Fernandez-Guerra, P.; Gonzalez-Ebsen, A.C.; Boonen, S.E.; Courraud, J.; Gregersen, N.; Mehlsen, J.; Palmfeldt, J.; Olsen, R.K.J.; Brinth, L.S. Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules 2021, 11, 961. https://doi.org/10.3390/biom11070961

AMA Style

Fernandez-Guerra P, Gonzalez-Ebsen AC, Boonen SE, Courraud J, Gregersen N, Mehlsen J, Palmfeldt J, Olsen RKJ, Brinth LS. Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules. 2021; 11(7):961. https://doi.org/10.3390/biom11070961

Chicago/Turabian Style

Fernandez-Guerra, Paula, Ana C. Gonzalez-Ebsen, Susanne E. Boonen, Julie Courraud, Niels Gregersen, Jesper Mehlsen, Johan Palmfeldt, Rikke K.J. Olsen, and Louise S. Brinth 2021. "Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study" Biomolecules 11, no. 7: 961. https://doi.org/10.3390/biom11070961

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