Sorensen, Bristol, Streib, Joanne E, Strand, Matthew et al. · The Journal of allergy and clinical immunology · 2003 · DOI
Researchers asked people with ME/CFS and healthy controls to exercise on a stationary bike, then tracked their symptoms and blood markers over the following week. They found that people with ME/CFS had a specific increase in a immune system marker called C4a six hours after exercise, and their fatigue and reduced activity worsened significantly, while healthy controls did not show these changes.
This study provides objective biological evidence that ME/CFS is associated with abnormal immune activation following exercise, supporting the validity of post-exertional malaise as a measurable physiological phenomenon rather than a subjective report alone. Identifying complement activation as a potential biomarker could advance diagnostic criteria and help explain the mechanism underlying symptom worsening after exertion.
This study does not prove that C4a elevation causes post-exertional symptoms—only that the two occur together. It also does not establish whether complement activation is specific to ME/CFS or present in other post-viral conditions, and the single exercise challenge does not capture the full complexity of how repeated exertion affects symptom burden over time.
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
Sorensen, Bristol, Streib, Joanne E, Strand, Matthew, Make, Barry, Giclas, Patricia C, Fleshner, Monika, et al. (2003). Complement activation in a model of chronic fatigue syndrome.. The Journal of allergy and clinical immunology. https://doi.org/10.1067/mai.2003.1615
BibTeX
@article{mecfsatlas-sorensen-2003-complement-activation,
author = {Sorensen, Bristol and Streib, Joanne E and Strand, Matthew and Make, Barry and Giclas, Patricia C and Fleshner, Monika and Jones, James F},
title = {Complement activation in a model of chronic fatigue syndrome.},
journal = {The Journal of allergy and clinical immunology},
year = {2003},
doi = {10.1067/mai.2003.1615},
note = {PubMed: 12897748},
url = {https://www.mecfsatlas.com/evidence/sorensen-2003-complement-activation},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/sorensen-2003-complement-activation
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