Ryback, Audrey A, Cowan, Graeme J M · Frontiers in immunology · 2025 · DOI
This study examined immune system cells called B cells in people with ME/CFS to see if the disease might be caused by chronic infections or autoimmune problems. Researchers compared blood samples from 25 patients with mild/moderate ME/CFS, 36 with severe ME/CFS, healthy people, and people with multiple sclerosis. They found that ME/CFS patients' B cells did not show the typical patterns expected if chronic infection or autoimmunity were the main cause, though they did notice a difference in the balance of certain antibody types in milder cases.
Understanding whether ME/CFS is driven by chronic infections or autoimmunity has major implications for treatment strategies. This study's direct examination of B-cell responses provides evidence against these leading hypotheses, potentially redirecting research toward other disease mechanisms. The observed IgM/IgG skewing suggests new biological leads that could improve diagnostic approaches and therapeutic understanding.
This study does not prove ME/CFS is not infectious or autoimmune in all cases—B-cell repertoire patterns alone cannot fully exclude these mechanisms, and findings in blood may not reflect immune responses in tissues. The lack of detected repertoire signatures does not rule out other immune abnormalities (T cells, innate immunity, cytokine dysregulation). The cross-sectional design cannot establish causation or temporal relationships between immune changes and 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
Ryback, Audrey A & Cowan, Graeme J M (2025). Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2025.1489312
BibTeX
@article{mecfsatlas-ryback-2025-deep-sequencing,
author = {Ryback, Audrey A and Cowan, Graeme J M},
title = {Deep sequencing of BCR heavy chain repertoires in myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Frontiers in immunology},
year = {2025},
doi = {10.3389/fimmu.2025.1489312},
note = {PubMed: 40034707},
url = {https://www.mecfsatlas.com/evidence/ryback-2025-deep-sequencing},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/ryback-2025-deep-sequencing
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