Is Chronic Fatigue Syndrome (CFS) An Autoimmune Condition?


Welcome to my blog post ‘Is Chronic Fatigue Syndrome (CFS) An Autoimmune Condition?’.

You may also be interested in the section of my blog dedicated to chronic fatigue syndrome, click here, in particular:

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Is Chronic Fatigue Syndrome (CFS) An Autoimmune Condition

ME/CFS disease onset is often reported to be triggered by infections and the link between infections and autoimmune diseases is well established. Although the exact pathogenesis is still unknown, the most plausible hypothesis is that dysregulation of immune system, autonomic nervous system and metabolic disturbances contribute to this complex syndrome, in which severe fatigue and cognitive impairment are a central feature. Stressful life events are frequently associated with disease onset concomitantly with a history of frequent recurrent infections, immune deficiency and autoimmunity. There are numerous studies showing immunological, genetic and metabolic alterations consistent with an autoimmune mechanism. Further, the identification of autoantibodies in ME/CFS patients and the clinical benefit associated with B cell depleting therapy provide strong evidence that, at least in a subset of ME/CFS patients, the disease has an autoimmune etiology.

CFS, Infections And Autoimmune Disease

Infection by various pathogens, including the Epstein-Barr virus (EBV), the human herpes virus (HHV)-6 and the human parvovirus B19, but also intracellular bacteria, are known as triggers of disease. In a subset of patients, ME/CFS begins with infectious mononucleosis and evidence for a potential role of EBV in ME/CFS comes from many studies. In 1984, DuBois et al. first described patients with mononucleosis syndrome suffering from long-lasting fatigue and serological evidence of EBV reactivation followed by a number of studies describing ME/CFS patients with serological evidence of chronic active EBV infection.

Infectious mononucleosis is known as a risk factor for various autoimmune diseases.

Several studies show homologies of EBV sequences with human autoantigens such as myelin basic protein for multiple sclerosis (MS)

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Autoantibodies And Chronic Fatigue Syndrome

Autoantibodies are antibodies (a type of protein), produced by the immune system, that is directed against one or more of our own proteins. Many autoimmune diseases (notably Lupus) are caused by such autoantibodies.

Several studies described autoantibodies in ME/CFS

Antinuclear antibodies (ANA) were found in one study in 68 % of ME/CFS patients.

Antibodies against:

  • The muscarinic M1 acetylcholine receptor (AChR)
  • ß1 and ß2 adrenergic receptors (AdR)
  • Thyroid peroxidase autoantibodies
  • Serotonin

Inflammation, Autoimmune Disease, And Chronic Fatigue Syndrome

Autoimmunity is associated with enhanced levels of circulating inflammatory molecules playing an important role in the pathogenesis of autoimmune diseases.

Elevated levels of cytokines (inflammatory molecules) have been reported for CFS in several studies.

Comorbidity with autoimmune diseases

Comorbidity of ME/CFS with various autoimmune or immune-mediated diseases including fibromyalgia (FM), Hashimoto’s thyroiditis and POTS is observed. Especially for FM there is considerable overlap with up to 77% of patients fulfilling disease criteria for both CFS and FM. FM is characterized by chronic widespread pain and is common in autoimmune diseases with around 50% of prevalence in patients with Rheumatoid Arthritis and Lupus.

Summary of ‘Is Chronic Fatigue Syndrome (CFS) An Autoimmune Condition?’:

  • The pathogenesis of ME/CFS is multifactorial, and immunological and environmental factors play a role.
  • Autoimmune mechanisms can be linked with ME/CFS at least in a subset of patients.
  • Autoantibodies mostly against nuclear and neurotransmitter receptors are found in a subset of ME/CFS patients.
  • Immunomodulatory therapeutic strategies targeting autoantibodies may be beneficial and should be pursued.

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References of ‘Is Chronic Fatigue Syndrome (CFS) An Autoimmune Condition?:

  1. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease: click here.
  2. IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression: click here.
  3. The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs): click here.
  4. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation: click here.
  5. A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors: click here.
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