A Proposed Mechanism for ME/CFS Invoking Macrophage FcγRI and Interferon Gamma

Evidence bearing on possible mechanisms for the clinical syndrome of ME/CFS is reviewed. Potential implications of disease onset and course, age profile, female predominance, relation to infection, failure of treatment with rituximab, absence of inflammation, myalgia, and possible nervous system involvement are considered. These implications are used to argue for a hypothesis that centres on a form of persistent, inappropriate, ‘neuroimmune over-responsiveness’ mediated primarily by T lymphocyte-macrophage interaction but influenced by IgG antibody binding to the gamma interferon-inducible high affinity immunoglobulin receptor FcγRI. This proposed mechanism could explain why the illness resembles post-infective T cell-mediated autoinflammatory syndromes in age of onset and time course but has a female preponderance similar to autoantibody-mediated disease.