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.

中文翻译：

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肌性脑脊髓炎/慢性疲劳综合症（ME / CFS）的病理生理学统一假设：对ß2-肾上腺素能受体自身抗体的发现的认识。

肌性脑脊髓炎或慢性疲劳综合症（CFS / ME）是一种复杂且严重致残的疾病，患病率为0.3％，未经批准的治疗方法，因此非常需要医疗。感染后，患者会遭受严重的中枢和肌肉疲劳，慢性疼痛，认知障碍以及免疫和自主神经功能障碍。尽管CFS / ME的病因尚未解决，但有许多证据表明自身抗体介导的免疫和自主神经系统功能异常。我们在一部分CFS / ME患者中发现ß2肾上腺素能受体（ß2AdR）和M3乙酰胆碱受体抗体升高。由于ß2AdR和M3乙酰胆碱受体都是重要的血管扩张剂，因此我们预期它们的功能紊乱会导致血管收缩和低氧血症。血液循环障碍和氧气供应不足可能导致ME / CFS的许多症状。关于ME / CFS中血管功能障碍的报道一致。在各种研究中，ME / CFS已显示出肌肉和大脑的灌注不足，并且与疲劳有关。ME / CFS中的代谢变化也符合缺氧和缺血的概念。在此，我们基于针对ß2AdR和M3乙酰胆碱受体的功能异常的自身抗体，尝试为ME / CFS的复杂发病机制开发统一的工作概念，并将其推断为ME / CFS的病理生理学，而无需自身免疫性发病机制。ME / CFS中的代谢变化也符合缺氧和缺血的概念。在此，我们基于针对ß2AdR和M3乙酰胆碱受体的功能异常的自身抗体的存在，尝试为ME / CFS的复杂发病机制开发一个统一的工作概念，并将其推断为ME / CFS的病理生理学，而无需自身免疫性发病机制。ME / CFS中的代谢变化也符合缺氧和缺血的概念。在此，我们基于针对ß2AdR和M3乙酰胆碱受体的功能异常的自身抗体的存在，尝试为ME / CFS的复杂发病机制开发一个统一的工作概念，并将其推断为ME / CFS的病理生理学，而无需自身免疫性发病机制。