Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-08-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.015989 |
| _version_ | 1818775135823331328 |
|---|---|
| author | Isabella Kharraziha Jonas Axelsson Fabrizio Ricci Giuseppe Di Martino Margaretha Persson Richard Sutton Artur Fedorowski Viktor Hamrefors |
| author_facet | Isabella Kharraziha Jonas Axelsson Fabrizio Ricci Giuseppe Di Martino Margaretha Persson Richard Sutton Artur Fedorowski Viktor Hamrefors |
| author_sort | Isabella Kharraziha |
| collection | DOAJ |
| description | 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 α1 receptor, adrenergic β2 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 α1 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 α1 receptor is associated with orthostatic symptoms severity in patients with POTS. |
| first_indexed | 2024-12-18T10:52:14Z |
| format | Article |
| id | doaj.art-a3ee25a06b494360984c17add84d04f4 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-18T10:52:14Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-a3ee25a06b494360984c17add84d04f42022-12-21T21:10:26ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-08-0191510.1161/JAHA.120.015989Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia SyndromeIsabella Kharraziha0Jonas Axelsson1Fabrizio Ricci2Giuseppe Di Martino3Margaretha Persson4Richard Sutton5Artur Fedorowski6Viktor Hamrefors7Department of Clinical Sciences Lund University Malmö SwedenDepartment of Stem Cell Therapy and Apheresis Karolinska University Hospital Stockholm SwedenDepartment of Clinical Sciences Lund University Malmö SwedenDepartment of Medicine and Ageing Sciences "G. d'Annunzio" University Chieti ItalyDepartment of Clinical Sciences Lund University Malmö SwedenDepartment of Clinical Sciences Lund University Malmö SwedenDepartment of Clinical Sciences Lund University Malmö SwedenDepartment of Clinical Sciences Lund University Malmö SwedenBackground 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 α1 receptor, adrenergic β2 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 α1 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 α1 receptor is associated with orthostatic symptoms severity in patients with POTS.https://www.ahajournals.org/doi/10.1161/JAHA.120.015989adrenergic receptorsautoimmunityG protein–coupled receptorsorthostatic intolerancepostural orthostatic tachycardia syndrome |
| spellingShingle | Isabella Kharraziha Jonas Axelsson Fabrizio Ricci Giuseppe Di Martino Margaretha Persson Richard Sutton Artur Fedorowski Viktor Hamrefors Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease adrenergic receptors autoimmunity G protein–coupled receptors orthostatic intolerance postural orthostatic tachycardia syndrome |
| title | Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome |
| title_full | Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome |
| title_fullStr | Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome |
| title_full_unstemmed | Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome |
| title_short | Serum Activity Against G Protein–Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome |
| title_sort | serum activity against g protein coupled receptors and severity of orthostatic symptoms in postural orthostatic tachycardia syndrome |
| topic | adrenergic receptors autoimmunity G protein–coupled receptors orthostatic intolerance postural orthostatic tachycardia syndrome |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.015989 |
| work_keys_str_mv | AT isabellakharraziha serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT jonasaxelsson serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT fabrizioricci serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT giuseppedimartino serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT margarethapersson serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT richardsutton serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT arturfedorowski serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome AT viktorhamrefors serumactivityagainstgproteincoupledreceptorsandseverityoforthostaticsymptomsinposturalorthostatictachycardiasyndrome |