Document Type

Article

Publication Date

2-21-2024

Comments

This article is the author's final published version in Nature Communications, Volume 15, 2024, Article number 907.

The published version is available at https://doi.org/10.1038/s41467-024-45107-3. This is a U.S. Government work and not under copyright protection in the US

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

41467_2024_45107_MOESM1_ESM.pdf (31278 kB)
Supplementary Information

41467_2024_45107_MOESM2_ESM.pdf (748 kB)
Peer Review File

41467_2024_45107_MOESM3_ESM.pdf (121 kB)
Description of Additional Supplementary Files

41467_2024_45107_MOESM4_ESM.zip (2225 kB)
Supplementary Data 1-24

41467_2024_45107_MOESM5_ESM.docx (99 kB)
Reporting Summary

Language

English

Share

COinS