James, Lisa M, Georgopoulos, Apostolos P · Neuroscience insights · 2022 · DOI
This review explores why some people develop long-lasting illnesses after exposure to viruses or bacteria, while others recover normally. The researchers propose that certain infections may persist in the body longer in people with specific immune system markers (HLA types), potentially causing ongoing damage to the brain and other organs. They suggest this mechanism might explain symptoms seen in ME/CFS, long-COVID, and Gulf War Illness.
Understanding why some ME/CFS patients develop persistent symptoms while others improve could identify which individuals are at risk for chronic disease progression. If the PA hypothesis is correct, it would support the biological basis of ME/CFS and suggest potential therapeutic targets (such as immune modulation or antigen clearance) that could improve treatment strategies. This framework also connects ME/CFS mechanistically to other well-recognized post-infection conditions, potentially strengthening research and clinical recognition of the disease.
This is a theoretical review, not original research, so it does not provide direct evidence that persistent antigens actually cause ME/CFS or establish causation rather than correlation. The paper does not demonstrate that HLA-antigen incongruence is the primary mechanism in ME/CFS patients, nor does it prove that all ME/CFS cases involve persistent antigens. Individual patient studies measuring actual antigen levels and HLA types are needed to test these propositions.
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
James, Lisa M & Georgopoulos, Apostolos P (2022). At the Root of 3 "Long" Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome.. Neuroscience insights. https://doi.org/10.1177/26331055221114817
BibTeX
@article{mecfsatlas-james-2022-root-long,
author = {James, Lisa M and Georgopoulos, Apostolos P},
title = {At the Root of 3 "Long" Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome.},
journal = {Neuroscience insights},
year = {2022},
doi = {10.1177/26331055221114817},
note = {PubMed: 35910083},
url = {https://www.mecfsatlas.com/evidence/james-2022-root-long},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/james-2022-root-long
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