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. 2021 Aug 19;10(16):3675.
doi: 10.3390/jcm10163675.

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

Helma Freitag  1 , Marvin Szklarski  1 , Sebastian Lorenz  1 , Franziska Sotzny  1 , Sandra Bauer  1 , Aurélie Philippe  2 , Claudia Kedor  1 , Patricia Grabowski  1 , Tanja Lange  3 , Gabriela Riemekasten  3 , Harald Heidecke  4 , Carmen Scheibenbogen  1   5
Affiliations

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

Helma Freitag et al. J Clin Med. .

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.

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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.
See this image and copyright information in PMC

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