Ikuta, Kazufumi, Yamada, Takeshi, Shimomura, Tokio et al. · Microbes and infection · 2003 · DOI
This study tested whether certain viral infections and immune system markers are linked to ME/CFS. Researchers measured a protein called 2-5AS in blood cells from ME/CFS patients in Japan and compared it to healthy people. They found that ME/CFS patients had higher levels of this immune marker than healthy controls, and some patients showed signs of past infections with Epstein-Barr virus or another bacteria.
This research provides potential laboratory markers (2-5AS activity) that could aid in diagnosing ME/CFS and suggests viral infections may play a role in disease pathogenesis. Understanding immune dysregulation associated with viral reactivation could inform future therapeutic targets.
This study does not prove that EBV or C. burnetii cause ME/CFS—it only shows associations in some patients. The wide variation between the two hospitals (86% vs 32% 2-5AS detection in patients) raises questions about whether results reflect true biological differences or methodological variation. Elevated 2-5AS may be a consequence rather than a cause of ME/CFS.
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
Ikuta, Kazufumi, Yamada, Takeshi, Shimomura, Tokio, Kuratsune, Hirohiko, Kawahara, Ryuzo, Ikawa, Shiro, et al. (2003). Diagnostic evaluation of 2', 5'-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan.. Microbes and infection. https://doi.org/10.1016/j.micinf.2003.07.002
BibTeX
@article{mecfsatlas-ikuta-2003-diagnostic-evaluation,
author = {Ikuta, Kazufumi and Yamada, Takeshi and Shimomura, Tokio and Kuratsune, Hirohiko and Kawahara, Ryuzo and Ikawa, Shiro and Ohnishi, Eiko and Sokawa, Yoshihiro and Fukushi, Hideto and Hirai, Katsuya and Watanabe, Yasuyoshi and Kurata, Takeshi and Kitani, Teruo and Sairenji, Takeshi},
title = {Diagnostic evaluation of 2', 5'-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan.},
journal = {Microbes and infection},
year = {2003},
doi = {10.1016/j.micinf.2003.07.002},
note = {PubMed: 14554250},
url = {https://www.mecfsatlas.com/evidence/ikuta-2003-diagnostic-evaluation},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/ikuta-2003-diagnostic-evaluation
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