Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 15;131(14):e150377.
doi: 10.1172/JCI150377.

Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Øystein Fluge  1   2 , Karl J Tronstad  3 , Olav Mella  1   2
Affiliations
Review

Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Øystein Fluge et al. J Clin Invest. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: Haukeland University Hospital has patents on the issue of B cell depletion therapy for chronic fatigue syndrome (ME/CFS), no. PCT/EP2020/074186. ØF and OM are mentioned as inventors in these applications.

Figures

Figure 1
Figure 1. Proposed model for ME/CFS pathomechanisms.
We suggest three principal steps underlie the initiation and maintenance of ME/CFS. (i) Immune response after infection serves as a triggering event, with a role for B cells/plasma cells and autoantibodies in the underlying pathology. (ii) The vascular system and possibly GPCRs are potential targets for autoantibodies, which may affect endothelium or neurovascular control and autonomic small nerve fibers. The autoantibodies could be pathogenic IgGs or functional autoantibodies that normally occur after infection, but persist and fail to resolve over time. This disturbed homeostasis involves endothelial dysfunction in large and small arteries, impaired venous return and preload failure, and arteriovenous shunting, presumed to result in impaired autoregulation of blood flow and tissue hypoxia on exertion. (iii) Secondary compensatory efforts may add to the clinical presentation and symptoms. They include autonomic adaptations, often with increased sympathetic tone, and metabolic adaptations aiming to restore energy supply. Possible strategies for clinical trials targeting these pathways are also indicated.
See this image and copyright information in PMC

References

    1. Steiner S, et al. Autoimmunity-related risk variants in PTPN22 and CTLA4 are associated with ME/CFS with infectious onset. Front Immunol. 2020;11:578. - PMC - PubMed
    1. Sato W, et al. Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome. Brain Behav Immun. doi: 10.1016/j.bbi.2021.03.023. [published online March 29, 2021.]. - DOI - PubMed
    1. Chang CM, et al. Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults. Cancer. 2012;118(23):5929–5936. doi: 10.1002/cncr.27612. - DOI - PMC - PubMed
    1. Milivojevic M, et al. Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS. PLoS One. 2020;15(7):e0236148. doi: 10.1371/journal.pone.0236148. - DOI - PMC - PubMed
    1. Nguyen CB, et al. Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. J Transl Med. 2017;15(1):102. doi: 10.1186/s12967-017-1201-0. - DOI - PMC - PubMed

Publication types

MeSH terms