Ruiz-Pablos, Manuel, Paiva, Bruno, Zabaleta, Aintzane · Frontiers in immunology · 2025 · DOI
This review examines how certain genes related to immune system recognition (HLA genes) might make some people more susceptible to autoimmune diseases and conditions like ME/CFS. These genes were originally helpful in protecting our ancestors from infections, but in today's environment they may cause the immune system to overreact. The authors suggest that modern stressors like infections, vaccines, and obesity might trigger this hyperactive immune response in people carrying these genes.
This review provides a biological framework for understanding ME/CFS within the broader context of autoimmune and post-infectious conditions, potentially explaining why certain individuals develop ME/CFS after infections or other triggers. If the proposed HLA-driven immune hyperreactivity model is correct, HLA profiling could eventually help identify at-risk populations and guide targeted treatments for ME/CFS patients.
This is a theoretical review, not an original research study with patient data or experimental evidence, so it does not prove that HLA genes directly cause ME/CFS or confirm the proposed mechanisms in ME/CFS patients specifically. The authors note that evidence linking these ancestral haplotypes to Long COVID, ME/CFS, and post-vaccination syndromes remains limited. The review cannot establish causation or rule out other genetic and environmental factors contributing to ME/CFS development.
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 →
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