Shetzline, Susan E, Martinand-Mari, Camille, Reichenbach, Nancy L et al. · Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2002 · DOI
Researchers found that ME/CFS patients have a smaller, altered form of a protein called RNase L in their immune cells compared to healthy people. This smaller protein (37-kDa) appears to work similarly to the normal-sized protein (80-kDa) in healthy controls, particularly in how it binds to immune signaling molecules. This discovery suggests that ME/CFS may involve a structural change in this immune system protein.
Identifying structural abnormalities in RNase L—a key component of the antiviral interferon response—provides molecular evidence that ME/CFS involves dysregulation of immune signaling pathways. This work supports the biological basis of ME/CFS and may help explain the immune dysfunction observed in the disease, potentially opening avenues for targeted therapies.
This study does not prove that the 37-kDa RNase L variant causes ME/CFS; it only demonstrates an association. The study does not show whether this protein variant directly contributes to symptoms, whether it is present in all ME/CFS patients, or how the variant arises mechanistically. Cross-sectional biochemical characterization alone cannot establish causality or determine if the variant is primary or secondary to disease processes.
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
Shetzline, Susan E, Martinand-Mari, Camille, Reichenbach, Nancy L, Buletic, Zivjena, Lebleu, Bernard, Pfleiderer, Wolfgang, et al. (2002). Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome.. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. https://doi.org/10.1089/10799900252952235
BibTeX
@article{mecfsatlas-shetzline-2002-structural-functional,
author = {Shetzline, Susan E and Martinand-Mari, Camille and Reichenbach, Nancy L and Buletic, Zivjena and Lebleu, Bernard and Pfleiderer, Wolfgang and Charubala, Ramamurthy and De Meirleir, Kenny and De Becker, Pascale and Peterson, Daniel L and Herst, C V T and Englebienne, Patrick and Suhadolnik, Robert J},
title = {Structural and functional features of the 37-kDa 2-5A-dependent RNase L in chronic fatigue syndrome.},
journal = {Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research},
year = {2002},
doi = {10.1089/10799900252952235},
note = {PubMed: 12034027},
url = {https://www.mecfsatlas.com/evidence/shetzline-2002-structural-functional},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/shetzline-2002-structural-functional
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