ME/CFS Research :: Theories and Hypotheses

Theories and Hypotheses

This page features a curated list of published theories and hypotheses for ME/CFS and related conditions. Rather than an exhaustive list of every conceivable hypothesis, only the best and most well-researched ideas will be listed here.

For ME/CFS

• "Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)"
  J Clin Invest. (Fluge 2021)
  • Editor's Summary: The authors suggest three steps underlie the initiation and maintenance of ME/CFS. First, an immune response after infection is a trigger for B cells/plasma cells and autoantibodies. Second, the autoantibodies target the vascular system and possibly GPCRs, which may affect endothelium or neurovascular control and autonomic small nerve fibers. This causes endothelial dysfunction in large and small arteries, impaired venous return and preload failure, and arteriovenous shunting, presumed to result in impaired autoregulation of blood flow and tissue hypoxia on exertion. Finally, compensatory efforts add to the clinical presentations with autonomic adaptations, often with increased sympathetic tone, and metabolic adaptations.
• "Insights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"
  Chest. (Joseph 2021)
  • Editor's Summary: This paper theorizes that exercise intolerance and orthostatic intolerance are due to peripheral neurovascular dysregulation. This is caused by either impaired venous return and/or impaired peripheral oxygen extraction. In some patients, small-fiber neuropathic dysregulation results in microvascular dilation, which causes shunting of oxygenated blood from capillary beds and reducing cardiac return. Additionally, the authors claim their findings are not consistent with deconditioning, and that their work "definitively eliminates" a deconditioning explanation for the symptoms of ME/CFS.
• "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease"
  Autoimmune Rev. (Sotzny 2018)
  • Abstract: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.

For Similar or Related Conditions

• "Epstein–Barr virus as a potentiator of autoimmune diseases"
  Nat Rev Rheumatol (Robinson 2024)
• "CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis"
  Autoimmune Dis. (Pender 2012)