Humer, Bart, Dik, Willem A, Versnel, Marjan A · Frontiers in immunology · 2025 · DOI
This review explores how a single severe infection might trigger long-term changes in the immune system that could lead to ME/CFS. After infection, immune cells can become 'trained' to overreact to future triggers, potentially causing the chronic symptoms patients experience. The researchers suggest this overactive immune response might explain why about 60% of ME/CFS patients remember getting sick before their symptoms started.
Understanding whether trained immunity contributes to ME/CFS pathogenesis could explain why infections precede symptom onset in many patients and why symptoms persist despite pathogen clearance. This mechanism might guide future diagnostic and therapeutic strategies targeting immune cell reprogramming rather than active infection.
This review does not establish that trained immunity causes ME/CFS—it presents a hypothesis supported by indirect evidence from other post-infectious diseases. The review cannot prove causation, cannot quantify how frequently trained immunity occurs in ME/CFS patients specifically, and does not report novel experimental validation in ME/CFS populations. Trained immunity may be one factor among multiple contributing mechanisms.
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 →
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Primary citation
Humer, Bart, Dik, Willem A, & Versnel, Marjan A (2025). Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2025.1483764
BibTeX
@article{mecfsatlas-humer-2025-advocating-role,
author = {Humer, Bart and Dik, Willem A and Versnel, Marjan A},
title = {Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review.},
journal = {Frontiers in immunology},
year = {2025},
doi = {10.3389/fimmu.2025.1483764},
note = {PubMed: 40201181},
url = {https://www.mecfsatlas.com/evidence/humer-2025-advocating-role},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/humer-2025-advocating-role
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