Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients - A validation study in plasma and cerebrospinal  fluid from two Swedish cohorts

Abstract

Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (Systemic Exertion Intolerance Disorder), is a disabling and often  long-lasting disease that can drastically impair quality of life and  physical/social functioning of the patients. Underlying pathological mechanisms  are to a large extent unknown, but the presence of autoantibodies, cytokine  pattern deviations and the presentation of cognitive and autonomic nervous system  related symptoms provide evidence for ME being an immunological disorder with  elements of autoimmunity. Increased levels of autoantibodies binding to  adrenergic and muscarinic receptors in ME-patients have been reported. It is  hypothesized that these autoantibodies have pathological significance and  contribute to the ME-specific symptoms, however, these observations need to be  validated. This study was designed to investigate potential differences in  adrenergic and muscarinic receptor autoantibody levels in plasma and  cerebrospinal fluid (CSF) samples between ME patients and gender and age-matched  healthy controls, and to correlate the autoantibody levels to disease severity.  We collected bodyfluids and health-related questionnaires from two Swedish ME  cohorts, plasma and CSF from one of the cohorts (n ​= ​24), only plasma from the  second cohort (n ​= ​24) together with plasma samples (n ​= ​24) and CSF  (n ​= ​6) from healthy controls. All samples were analysed for IgG autoantibodies  directed against Alpha- (α1, α2) and Beta- (β1-3) adrenergic receptors and  Muscarinic (M) 1-5 acetylcholine receptors using an ELISA technique. The  questionnaires were used as measures of disease severity. Significant increases  in autoantibody levels in ME patients compared to controls were found for M3 and  M4 -receptors in both cohorts and β1, β2, M3 and M4-receptors in one cohort. No  significant correlations were found between autoantibody levels and disease  severity. No significant levels of autoantibodies were detected in the CSF  samples. These findings support previous findings that there exists a general  pattern of increased antibody levels to adrenergic and muscarinic receptors  within the ME patient group. However, the role of increased adrenergic and  muscarinic receptor autoantibodies in the pathogenesis of ME is still uncertain  and further research is needed to evaluate the clinical significance of these  findings.