Serum activity against G protein-coupled receptors and severity of orthostatic symptoms in postural orthostatic tachycardia syndrome
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Background: Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein–coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell‐based assay. Methods and Results: Forty‐eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10‐item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein–coupled receptor: adrenergic α 1 receptor, adrenergic β 2 receptor, cholinergic muscarinic type 2 receptor, and opioid receptor‐like 1 were treated with sera from all patients. Receptor response was analyzed using a β‐arrestin–linked transcription factor driving transgenic β‐lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein–coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls ( P <0.01 for all). The area under the curve was 0.88 (0.80–0.97, P <0.001) combining all 4 receptors. Adrenergic α 1 receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity, P =0.009) and with reduced tolerability for prolonged standing ( P =0.037) and walking for short ( P =0.042) or long ( P =0.001) periods. All 4 receptors were associated with vision problems ( P <0.05 for all). Conclusions: Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum‐mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α 1 receptor is associated with orthostatic symptoms severity in patients with POTS.
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Serum-mediated adrenergic α1 receptor activity had a strong association with orthostatic symptoms independent of the hemodynamic response.
“Serum-mediated adrenergic α1 receptor activity had a strong association with orthostatic symptoms independent of the hemodynamic response.”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Kharraziha et al., 2020
Patients with POTS had circulating proteins activating cardiovascular ADRA1, ADRB2, CHRM2, and nociception-related OPRL1 to a higher degree compared with controls.
“Results from this study indicated the presence of circulating proteins activating cardiovascular ADRA1 (adrenergic α1 receptor), ADRB2 (adrenergic β2 receptor), CHRM2 (cholinergic muscarinic type 2 receptor), and nociception-related OPRL1 (opioid receptor-like 1) in patients with POTS to a higher degree compared with controls.”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Kharraziha et al., 2020
Activation of ADRB2, CHRM2, OPRL1 was not significantly associated with overall OHQ symptom scores.
“Activation of ADRB2, CHRM2, OPRL1 was not significantly associated with overall OHQ symptom scores.”
From Self-reported symptom burden in postural orthostatic tachycardia syndrome (POTS): A narrative review of observational and interventional studies (2023) · cites this paper as Kharraziha et al., 2020
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“Mean ± SD 6.0 ± 18.6 42 Kharraziha et al., 2020.”
Influential
- Authors
- Kharraziha, I., Axelsson, J., Ricci, F., Di Martino, G., Persson, M., Sutton, R., Fedorowski, A., & Hamrefors, V.
- Affiliations
- Lund University (SE)
- Karolinska University Hospital (SE)
- Department of Medicine and Ageing Sciences "G. d'Annunzio" University Chieti Italy
- Corresponding author
- Kharraziha, Isabella
- ORCID
- Venue
- Journal of the American Heart Association
- Published
- 2020-08-04
- Volume
- 9
- Issue
- 15
- Pages
- e015989-e015989
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC7792263
- OpenAlex
- W3045736288
- Cited by
- 54
- References
- 5
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 15 · 2022: 11 · 2021: 9 · 2020: 1
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- postural orthostatic tachycardia syndrome, G protein-coupled receptors, muscarinic receptors, opioid receptor-like 1, orthostatic intolerance, orthostatic symptoms, vision problems
- MeSH terms
- Adult, Female, Humans, Male, Surveys and Questionnaires, Severity of Illness Index, Autoimmunity, Case-Control Studies, Receptors, G-Protein-Coupled, Postural Orthostatic Tachycardia Syndrome
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