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Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome

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机构: [1]National Institute of Neurological Diseases and Stroke (NINDS), Bethesda, MD, USA [2]National Heart, Lung and Blood Institute (NHLBI), Bethesda, MD, USA [3]National Institute of Diabetes, Digestion, and Kidney Disease (NIDDK), Bethesda, MD, USA [4]NIH Center for Human Immunology, Autoimmunity, andInflammation (CHI), Bethesda, MD, USA [5]NIH Clinical Center (CC), Bethesda, MD, USA [6]National Institute of Mental Health (NIMH), Bethesda, MD, USA [7]National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, MD, USA [8]Texas A&M School of Engineering Medicine, College Station, TX, USA [9]Affiliated Hospital of North Sichuan Medical College, Sichuan, China [10]George Washington University Hospital, District of Columbia, Washington, DC, USA [11]Allegheny General Hospital, Pittsburgh, PA, USA [12]National Institute on Drug Abuse (NIDA), Bethesda, MD, USA [13]National Institute of Aging (NIA), Baltimore,MD, USA [14]National Institute of Environmental Health Sciences (NIEHS), Chapel Hill, NC, USA [15]Sidney Kimmel Medical College, Philadelphia, PA, USA [16]National Institute of Nursing Research (NINR), Bethesda, MD, USA [17]National Institute of Allergy and Infectious Disease (NIAID), Bethesda, MD, USA [18]National Center for Complementary and Integrative Health (NCCIH), Bethesda, MD, USA [19]National Institute of Arthritis and Musculoskeletal and SkinDiseases (NIAMS), Bethesda, MD, USA [20]National Cancer Institute (NCI), Bethesda, MD, USA [21]Columbia University Medical Center, New York, NY, USA [22]University of Colorado School of Medicine, Boulder, CO, USA [23]Clínica Alemana Universidad del Desarrollo, Santiago, Chile [24]Oakland University WilliamBeaumont School of Medicine, Rochester, NY, USA
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Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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第一作者机构: [1]National Institute of Neurological Diseases and Stroke (NINDS), Bethesda, MD, USA
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