Heng, Benjamin, Gunasegaran, Bavani, Krishnamurthy, Shivani et al. · Cell reports. Medicine · 2025 · DOI
This study examined blood samples from ME/CFS patients and healthy people to understand what goes wrong in the body. Researchers found that immune cells in ME/CFS patients are struggling to make energy (ATP), the fuel that powers our cells. The immune system also showed signs of being immature or worn out, and blood proteins related to clotting and blood vessel problems were elevated, suggesting blood vessel dysfunction may contribute to ME/CFS symptoms.
This study provides concrete biological evidence that ME/CFS involves measurable abnormalities in energy production, immune function, and blood vessel health—supporting the view that ME/CFS is a real physiological disease, not psychological. These findings could eventually lead to diagnostic tests and targeted treatments addressing the underlying causes rather than just managing symptoms.
This study does not prove that energy metabolism problems, immune changes, or vascular dysfunction directly cause ME/CFS symptoms or whether these are primary or secondary consequences of the illness. It identifies associations in one point-in-time snapshot and cannot establish whether these biomarkers change over disease course or predict treatment response.
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
Heng, Benjamin, Gunasegaran, Bavani, Krishnamurthy, Shivani, Bustamante, Sonia, Pires, Ananda Staats, Chow, Sharron, et al. (2025). Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction.. Cell reports. Medicine. https://doi.org/10.1016/j.xcrm.2025.102514
BibTeX
@article{mecfsatlas-heng-2025-mapping-complexity,
author = {Heng, Benjamin and Gunasegaran, Bavani and Krishnamurthy, Shivani and Bustamante, Sonia and Pires, Ananda Staats and Chow, Sharron and Ahn, Seong Beom and Paul-Heng, Moumita and Maciver, Yolande and Smith, Kirsten and Tran, Denise P and Howley, Peter P and Bilgin, Ayse Aysin and Sharland, Alexandra and Schloeffel, Richard and Guillemin, Gilles J},
title = {Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction.},
journal = {Cell reports. Medicine},
year = {2025},
doi = {10.1016/j.xcrm.2025.102514},
note = {PubMed: 41406947},
url = {https://www.mecfsatlas.com/evidence/heng-2025-mapping-complexity},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/heng-2025-mapping-complexity
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