Souma, Bernard, Elremaly, Wesam, Akoume, Marie-Yvonne et al. · International journal of molecular sciences · 2026 · DOI
Researchers compared blood levels of two proteins—irisin and thrombospondin-1 (TSP-1)—in 92 ME/CFS patients and 44 healthy controls, measuring them before and after a physical stress test. They observed that ME/CFS patients had lower baseline irisin levels and a weaker response to the stress challenge, while those with more severe symptoms showed elevated levels of both proteins. The study proposes that TSP-1 may interfere with irisin's normal signaling, potentially contributing to energy problems in ME/CFS, but these findings are preliminary and require validation in larger studies.
This study identifies a candidate molecular dysregulation—the irisin-TSP-1 axis—potentially relevant to energy metabolism failure in ME/CFS. The association between TSP-1 elevation and symptom severity, combined with proposed HSP90α and αvβ5 dependence, offers a measurable biomarker framework and potential therapeutic target for future research. However, cross-sectional data cannot establish whether these protein changes drive PEM or reflect a consequence of the disease.
This cross-sectional design does not establish causation; it does not confirm that irisin-TSP-1 dysregulation causes PEM or metabolic dysfunction. It does not validate the proposed HSP90α-αvβ5 mechanism in living ME/CFS patients (in vitro data only). The findings require replication in a larger, prospective cohort and do not yet support any clinical intervention.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Souma, Bernard, Elremaly, Wesam, Akoume, Marie-Yvonne, Elbakry, Mohamed, Godbout, Christian, & Moreau, Alain (2026). Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.. International journal of molecular sciences. https://doi.org/10.3390/ijms27114770
BibTeX
@article{mecfsatlas-souma-2026-irisin-signaling,
author = {Souma, Bernard and Elremaly, Wesam and Akoume, Marie-Yvonne and Elbakry, Mohamed and Godbout, Christian and Moreau, Alain},
title = {Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.},
journal = {International journal of molecular sciences},
year = {2026},
doi = {10.3390/ijms27114770},
note = {PubMed: 42278300},
url = {https://www.mecfsatlas.com/evidence/souma-2026-irisin-signaling},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-06-14. https://www.mecfsatlas.com/evidence/souma-2026-irisin-signaling
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