Pasi, Annamaria, Bozzini, Sara, Carlo-Stella, Nicoletta et al. · Molecular medicine reports · 2011 · DOI
This study examined immune system genes called KIRs and their matching partners (HLA molecules) in people with ME/CFS. Researchers found that people with ME/CFS had an unusual pattern of these immune genes—specifically, more of a type called KIR3DS1 and fewer matching HLA partners for their receptors to recognize. The researchers suggest this mismatch might make it harder for the immune system to fight off infections, potentially allowing chronic infections to persist.
NK cell dysfunction is a recognized feature of ME/CFS, yet the genetic basis remains poorly understood. If genetic KIR-HLA mismatches genuinely impair antiviral immunity in ME/CFS patients, this could explain both the persistent pathogen hypothesis and individual variation in disease severity, potentially opening new diagnostic or therapeutic avenues.
This study does not prove that KIR-HLA polymorphisms cause ME/CFS—it only identifies associations in a small sample. The findings are correlational, not causal; it remains unknown whether these genetic patterns are primary drivers of disease or secondary consequences. Additionally, the study does not confirm the presence of persistent pathogens or demonstrate that the identified genetic patterns actually result in reduced NK cell function in these patients.
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
Pasi, Annamaria, Bozzini, Sara, Carlo-Stella, Nicoletta, Martinetti, Miryam, Bombardieri, Stefano, De Silvestri, Annalisa, et al. (2011). Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome.. Molecular medicine reports. https://doi.org/10.3892/mmr.2011.447
BibTeX
@article{mecfsatlas-pasi-2011-excess-activating,
author = {Pasi, Annamaria and Bozzini, Sara and Carlo-Stella, Nicoletta and Martinetti, Miryam and Bombardieri, Stefano and De Silvestri, Annalisa and Salvaneschi, Laura and Cuccia, Mariaclara},
title = {Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome.},
journal = {Molecular medicine reports},
year = {2011},
doi = {10.3892/mmr.2011.447},
note = {PubMed: 21468604},
url = {https://www.mecfsatlas.com/evidence/pasi-2011-excess-activating},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/pasi-2011-excess-activating
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