Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an acquired complex disease with patients suffering from the cardinal symptoms of  fatigue, post-exertional malaise (PEM), cognitive impairment, pain and autonomous  dysfunction. ME/CFS is triggered by an infection in the majority of patients.  Initial evidence for a potential role of natural regulatory autoantibodies (AAB)  to beta-adrenergic (AdR) and muscarinic acetylcholine receptors (M-AChR) in  ME/CFS patients comes from a few studies. METHODS: Here, we analyzed the  correlations of symptom severity with levels of AAB to vasoregulative AdR, AChR  and Endothelin-1 type A and B (ETA/B) and Angiotensin II type 1 (AT1) receptor in  a Berlin cohort of ME/CFS patients (n = 116) by ELISA. The severity of disease,  symptoms and autonomic dysfunction were assessed by questionnaires. RESULTS: We  found levels of most AABs significantly correlated with key symptoms of fatigue  and muscle pain in patients with infection-triggered onset. The severity of  cognitive impairment correlated with AT1-R- and ETA-R-AAB and severity of  gastrointestinal symptoms with alpha1/2-AdR-AAB. In contrast, the patients with  non-infection-triggered ME/CFS showed fewer and other correlations. CONCLUSION:  Correlations of specific AAB against G-protein-coupled receptors (GPCR) with  symptoms provide evidence for a role of these AAB or respective receptor pathways  in disease pathomechanism.