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.
Highlights
Myalgic encephalomyelitis (ME) means “muscle pain related to central nervous system inflammation” and was described in the 1950’s (Acheson, 1957; Galpine and Brady, 1957) as a complex, often severely disabling and chronic illness with unknown aetiology and pathological mechanism
We found significantly increased autoantibody levels for M3 and M4receptors within the SK-patients compared to controls and significantly increased autoantibody levels for β1, β2, M3 and M4 receptors in GCpatients compared to controls
These results validate the results from Scheibenbogen et al As a complement to prior research we found significantly increased levels of β1-autoantibodies in patients compared to controls and no detectable titres of muscarinic or adrenergic autoantibodies in cerebrospinal fluid, finding no evidence of intrathecal antibody production in the ME patient group
Summary
Myalgic encephalomyelitis (ME) means “muscle pain related to central nervous system inflammation” and was described in the 1950’s (Acheson, 1957; Galpine and Brady, 1957) as a complex, often severely disabling and chronic illness with unknown aetiology and pathological mechanism. Despite the seriousness of the illness, no specific diagnostic biomarkers or disease modifying treatments are available. The diagnosis is based on clinical criteria, such as the Canadian consensus criteria (CCC, 2003) (Carruthers et al, 2003) and the International consensus criteria (ICC, 2011) (Carruthers et al, 2011) or the more recent Institute of Medicine (IOM) criteria (2015) (Institute of Medicine, 2015). Post-exertional malaise (PEM) is central to the symptomatology and a required symptom for diagnosis in current diagnostic criteria, it is the significant worsening of disease symptoms upon physical or mental exertion. Other common symptoms include pain, headache, vertigo (orthostatic), unrefreshing sleep, muscle weakness, gastrointestinal problems, newly acquired drug/food allergies, recurrent throat pain, light sensitivity, flu like symptoms and several neurocognitive symptoms such as working memory impairment, concentration and information processing difficulties
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