A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies  against ß2-adrenergic receptors

Abstract

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (CFS/ME) is a complex and severely disabling disease with a prevalence of 0.3% and no approved treatment  and therefore a very high medical need. Following an infectious onset patients  suffer from severe central and muscle fatigue, chronic pain, cognitive  impairment, and immune and autonomic dysfunction. Although the etiology of CFS/ME  is not solved yet, there is numerous evidence for an autoantibody mediated  dysregulation of the immune and autonomic nervous system. We found elevated ß2  adrenergic receptor (ß2AdR) and M3 acetylcholine receptor antibodies in a subset  of CFS/ME patients. As both ß2AdR and M3 acetylcholine receptor are important  vasodilators, we would expect their functional disturbance to result in  vasoconstriction and hypoxemia. An impaired circulation and oxygen supply could  result in many symptoms of ME/CFS. There are consistent reports of vascular  dysfunction in ME/CFS. Muscular and cerebral hypoperfusion has been shown in  ME/CFS in various studies and correlated with fatigue. Metabolic changes in  ME/CFS are also in line with a concept of hypoxia and ischemia. Here we try to  develop a unifying working concept for the complex pathomechanism of ME/CFS based  on the presence of dysfunctional autoantibodies against ß2AdR and M3  acetylcholine receptor and extrapolate it to the pathophysiology of ME/CFS  without an autoimmune pathogenesis.