Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al. · medRxiv : the preprint server for health sciences · 2025 · DOI
This study found that people with ME/CFS may have an overactive immune system that responds too strongly to germs and infections. The research showed problems with how the body produces energy and manages inflammation, and these problems got worse after exercise in ME/CFS patients but not in healthy people. The findings suggest multiple biological systems are working abnormally in ME/CFS, which could help doctors develop better treatments.
Understanding the biological mechanisms underlying ME/CFS—particularly how immune activation, energy metabolism, and post-exertional malaise are interconnected—is crucial for developing targeted treatments. This study provides a comprehensive molecular framework that could guide development of therapeutic interventions and validate biomarkers for diagnosis and treatment monitoring.
This study does not prove causation—it identifies associations between biological abnormalities and ME/CFS symptoms. It is a preprint (not yet peer-reviewed) and mechanistic in nature, so results require independent replication in larger cohorts. The study does not establish which abnormalities are primary causes versus secondary consequences of the disease.
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
Che, Xiaoyu, Ranjan, Amit, Guo, Cheng, Zhang, Keming, Goldsmith, Rochelle, Levine, Susan, et al. (2025). Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.07.23.25332049
BibTeX
@article{mecfsatlas-che-2025-heightened-innate,
author = {Che, Xiaoyu and Ranjan, Amit and Guo, Cheng and Zhang, Keming and Goldsmith, Rochelle and Levine, Susan and Moneghetti, Kegan J and Zhai, Yali and Ge, Liner and Mishra, Nischay and Hornig, Mady and Bateman, Lucinda and Klimas, Nancy G and Montoya, Jose G and Peterson, Daniel L and Klein, Sabra L and Fiehn, Oliver and Komaroff, Anthony L and Lipkin, W Ian},
title = {Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.},
journal = {medRxiv : the preprint server for health sciences},
year = {2025},
doi = {10.1101/2025.07.23.25332049},
note = {PubMed: 40778181},
url = {https://www.mecfsatlas.com/evidence/che-2025-heightened-innate},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/che-2025-heightened-innate
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