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

Helma Freitag, Marvin Szklarski, Sebastian Lorenz, Franziska Sotzny, Sandra Bauer, Aurélie Philippe, Claudia Kedor, Patricia Grabowski, Tanja Lange, Gabriela Riemekasten, Harald Heidecke, Carmen Scheibenbogen, Helma Freitag, Marvin Szklarski, Sebastian Lorenz, Franziska Sotzny, Sandra Bauer, Aurélie Philippe, Claudia Kedor, Patricia Grabowski, Tanja Lange, Gabriela Riemekasten, Harald Heidecke, Carmen Scheibenbogen

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.

Keywords: G-protein-coupled receptor; adrenergic receptors; autoantibodies; autoimmunity; chronic fatigue syndrome; myalgic encephalomyelitis; vasoregulation.

Conflict of interest statement

H.H., managing director of CellTrend GmbH, holds a patent for the use of beta-adrenergic receptor antibodies in diagnosis of CFS. All other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Correlations between symptom severity and AAB/IgG ratios. Correlation analysis of AAB/IgG ratios with the severity of (A) fatigue, muscle pain, cognitive and immune symptom scores, physical functioning (SF-36) and Bell disability score and (B) with COMPASS 31 subdomains. Spearman correlation coefficients (r) are shown for patients with infection-triggered onset (black bars) and patients without infection-triggered onset (grey bars). Significant correlations prior to BH-correction are marked with asterisks (* p < 0.05, ** p < 0.01), correlations that remained significant after BH-correction are indicated by black-and-white striped bars.

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