Tokunaga, Keli, Sung, Alexander P, Tang, Jennifer J-J et al. · Work (Reading, Mass.) · 2020 · DOI
Researchers studied immune cells called monocytes in ME/CFS patients and compared them to both healthy unrelated people and to family members without ME/CFS. They found that monocytes were slightly elevated in ME/CFS patients compared to unrelated healthy people, but when they compared patients to their own family members without the illness, the difference disappeared. This suggests that including unaffected family members as comparison groups helps researchers avoid mistakenly identifying false biomarkers.
This research addresses a critical challenge in ME/CFS research: distinguishing true disease biomarkers from false positives caused by genetic or environmental factors shared within families. By proposing the inclusion of unaffected family members as controls, the authors provide a practical strategy for the field to accelerate biomarker discovery and avoid wasting resources pursuing non-specific findings.
This study does not prove that non-classical monocytes are unrelated to ME/CFS pathophysiology—only that they cannot serve as a specific biomarker for diagnosis. The findings are preliminary pilot data and do not establish causation or the underlying mechanism of immune dysfunction in ME/CFS. The small sample size and focus on one immune cell type limit generalizability.
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
Tokunaga, Keli, Sung, Alexander P, Tang, Jennifer J-J, Guglielmo, Michael J, Smith-Gagen, Julie, Bateman, Lucinda, et al. (2020). Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS.. Work (Reading, Mass.). https://doi.org/10.3233/WOR-203177
BibTeX
@article{mecfsatlas-tokunaga-2020-inclusion-family,
author = {Tokunaga, Keli and Sung, Alexander P and Tang, Jennifer J-J and Guglielmo, Michael J and Smith-Gagen, Julie and Bateman, Lucinda and Redelman, Doug D and Hudig, Dorothy},
title = {Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS.},
journal = {Work (Reading, Mass.)},
year = {2020},
doi = {10.3233/WOR-203177},
note = {PubMed: 32568152},
url = {https://www.mecfsatlas.com/evidence/tokunaga-2020-inclusion-family},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/tokunaga-2020-inclusion-family
Contribute
Private, reviewed by a human. Not a public comment thread.