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

Brian Walitt, Komudi Singh, Samuel R. LaMunion, Mark Hallett, Steve Jacobson, Kong Chen, Yoshimi Enose-Akahata, Richard Apps, Jennifer J. Barb, Patrick Bedard, Robert J. Brychta, Ashura Williams Buckley, Peter D. Burbelo, Brice Calco, Brianna Cathay, Li Chen, Snigdha Chigurupati, Jinguo Chen, Foo Cheung, Lisa M. K. Chin, Benjamin W. Coleman, Amber B. Courville, Madeleine S. Deming, Bart Drinkard, Li Rebekah Feng, Luigi Ferrucci, Scott A. Gabel, Angelique Gavin, David S. Goldstein, Shahin Hassanzadeh, Sean C. Horan, Silvina G. Horovitz, Kory R. Johnson, Anita Jones Govan, Kristine M. Knutson, Joy D. Kreskow, Mark Levin, Jonathan J. Lyons, Nicholas Madian, Nasir Malik, Andrew L. Mammen, John A. McCulloch, Patrick M. McGurrin, Joshua D. Milner, Ruin Moaddel, Geoffrey A. Mueller, Amrita Mukherjee, Sandra Muñoz-Braceras, Gina Norato, Katherine Pak, Iago Pinal-Fernandez, Traian Popa, Lauren B. Reoma, Michael N. Sack, Farinaz Safavi, Leorey N. Saligan, Brian A. Sellers, Stephen Sinclair, Bryan Smith, Joseph Snow, Stacey Solin, Barbara J. Stussman, Giorgio Trinchieri, Sara A. Turner, C. Stephenie Vetter, Felipe Vial, Carlotta Vizioli, Ashley Williams, Shanna B. Yang and Avindra Nath ()
Additional contact information
Brian Walitt: National Institute of Neurological Diseases and Stroke (NINDS)
Komudi Singh: Lung and Blood Institute (NHLBI)
Samuel R. LaMunion: Digestion, and Kidney Disease (NIDDK)
Mark Hallett: National Institute of Neurological Diseases and Stroke (NINDS)
Steve Jacobson: National Institute of Neurological Diseases and Stroke (NINDS)
Kong Chen: Digestion, and Kidney Disease (NIDDK)
Yoshimi Enose-Akahata: National Institute of Neurological Diseases and Stroke (NINDS)
Richard Apps: Autoimmunity, and Inflammation (CHI)
Jennifer J. Barb: NIH Clinical Center (CC)
Patrick Bedard: National Institute of Neurological Diseases and Stroke (NINDS)
Robert J. Brychta: Digestion, and Kidney Disease (NIDDK)
Ashura Williams Buckley: National Institute of Mental Health (NIMH)
Peter D. Burbelo: National Institute of Dental and Craniofacial Research (NIDCR)
Brice Calco: National Institute of Neurological Diseases and Stroke (NINDS)
Brianna Cathay: Texas A&M School of Engineering Medicine
Li Chen: Affiliated Hospital of North Sichuan Medical College
Snigdha Chigurupati: George Washington University Hospital, District of Columbia
Jinguo Chen: Autoimmunity, and Inflammation (CHI)
Foo Cheung: Autoimmunity, and Inflammation (CHI)
Lisa M. K. Chin: NIH Clinical Center (CC)
Benjamin W. Coleman: Allegheny General Hospital
Amber B. Courville: Digestion, and Kidney Disease (NIDDK)
Madeleine S. Deming: NIH Clinical Center (CC)
Bart Drinkard: NIH Clinical Center (CC)
Li Rebekah Feng: National Institute on Drug Abuse (NIDA)
Luigi Ferrucci: National Institute of Aging (NIA)
Scott A. Gabel: National Institute of Environmental Health Sciences (NIEHS)
Angelique Gavin: National Institute of Neurological Diseases and Stroke (NINDS)
David S. Goldstein: National Institute of Neurological Diseases and Stroke (NINDS)
Shahin Hassanzadeh: Lung and Blood Institute (NHLBI)
Sean C. Horan: Sidney Kimmel Medical College
Silvina G. Horovitz: National Institute of Neurological Diseases and Stroke (NINDS)
Kory R. Johnson: National Institute of Neurological Diseases and Stroke (NINDS)
Anita Jones Govan: National Institute of Neurological Diseases and Stroke (NINDS)
Kristine M. Knutson: National Institute of Neurological Diseases and Stroke (NINDS)
Joy D. Kreskow: National Institute of Nursing Research (NINR)
Mark Levin: Lung and Blood Institute (NHLBI)
Jonathan J. Lyons: National Institute of Allergy and Infectious Disease (NIAID)
Nicholas Madian: National Center for Complementary and Integrative Health (NCCIH)
Nasir Malik: National Institute of Neurological Diseases and Stroke (NINDS)
Andrew L. Mammen: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
John A. McCulloch: National Cancer Institute (NCI)
Patrick M. McGurrin: National Institute of Neurological Diseases and Stroke (NINDS)
Joshua D. Milner: Columbia University Medical Center
Ruin Moaddel: National Institute of Aging (NIA)
Geoffrey A. Mueller: National Institute of Environmental Health Sciences (NIEHS)
Amrita Mukherjee: Autoimmunity, and Inflammation (CHI)
Sandra Muñoz-Braceras: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Gina Norato: National Institute of Neurological Diseases and Stroke (NINDS)
Katherine Pak: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Iago Pinal-Fernandez: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Traian Popa: National Institute of Neurological Diseases and Stroke (NINDS)
Lauren B. Reoma: National Institute of Neurological Diseases and Stroke (NINDS)
Michael N. Sack: Lung and Blood Institute (NHLBI)
Farinaz Safavi: National Institute of Neurological Diseases and Stroke (NINDS)
Leorey N. Saligan: National Institute of Nursing Research (NINR)
Brian A. Sellers: Autoimmunity, and Inflammation (CHI)
Stephen Sinclair: National Institute of Mental Health (NIMH)
Bryan Smith: National Institute of Neurological Diseases and Stroke (NINDS)
Joseph Snow: National Institute of Mental Health (NIMH)
Stacey Solin: NIH Clinical Center (CC)
Barbara J. Stussman: National Institute of Neurological Diseases and Stroke (NINDS)
Giorgio Trinchieri: National Cancer Institute (NCI)
Sara A. Turner: NIH Clinical Center (CC)
C. Stephenie Vetter: University of Colorado School of Medicine
Felipe Vial: Clínica Alemana Universidad del Desarrollo
Carlotta Vizioli: National Institute of Neurological Diseases and Stroke (NINDS)
Ashley Williams: Oakland University William Beaumont School of Medicine
Shanna B. Yang: NIH Clinical Center (CC)
Avindra Nath: National Institute of Neurological Diseases and Stroke (NINDS)

Nature Communications, 2024, vol. 15, issue 1, 1-29

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-45107-3

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