Hornig, Mady, Montoya, José G, Klimas, Nancy G et al. · Science advances · 2015 · DOI
This study found that people with ME/CFS have distinctive patterns of immune system markers in their blood, but only early in the disease. Researchers compared blood samples from 52 people with early-stage ME/CFS to 348 healthy people and 246 people with long-standing ME/CFS. The early-stage group showed heightened immune activity that was not present in people who had been sick longer, suggesting the disease's immune profile changes over time.
This research is significant because it identifies objective blood-based signatures that could enable earlier diagnosis of ME/CFS—a disease currently diagnosed only by clinical criteria. The finding that immune markers change with disease duration provides a biological explanation for why previous biomarker studies produced inconsistent results and suggests that sampling timing is critical for future diagnostic test development.
This study does not prove that these immune alterations cause ME/CFS or that they are sufficient for diagnosis on their own. The cross-sectional design means we cannot establish whether these immune changes persist in early-stage patients or how they predict outcomes. It also does not explain why immune signatures normalize in longer-duration cases or whether this represents true resolution or adaptive changes.
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
Hornig, Mady, Montoya, José G, Klimas, Nancy G, Levine, Susan, Felsenstein, Donna, Bateman, Lucinda, et al. (2015). Distinct plasma immune signatures in ME/CFS are present early in the course of illness.. Science advances. https://doi.org/10.1126/sciadv.1400121
BibTeX
@article{mecfsatlas-hornig-2015-distinct-plasma,
author = {Hornig, Mady and Montoya, José G and Klimas, Nancy G and Levine, Susan and Felsenstein, Donna and Bateman, Lucinda and Peterson, Daniel L and Gottschalk, C Gunnar and Schultz, Andrew F and Che, Xiaoyu and Eddy, Meredith L and Komaroff, Anthony L and Lipkin, W Ian},
title = {Distinct plasma immune signatures in ME/CFS are present early in the course of illness.},
journal = {Science advances},
year = {2015},
doi = {10.1126/sciadv.1400121},
note = {PubMed: 26079000},
url = {https://www.mecfsatlas.com/evidence/hornig-2015-distinct-plasma},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/hornig-2015-distinct-plasma
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