{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:34:33Z","timestamp":1793468073243,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">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\u2013coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell\u2010based assay.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Forty\u2010eight patients with POTS (aged 28.6\u00b110.5\u00a0years; 44 women) and 25 healthy individuals (aged 30.7\u00b18.6\u00a0years; 21 women) were included. The 10\u2010item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein\u2013coupled receptor: adrenergic \u03b1\n              <jats:sub>1<\/jats:sub>\n              receptor, adrenergic \u03b2\n              <jats:sub>2<\/jats:sub>\n              receptor, cholinergic muscarinic type 2 receptor, and opioid receptor\u2010like 1 were treated with sera from all patients. Receptor response was analyzed using a \u03b2\u2010arrestin\u2013linked transcription factor driving transgenic \u03b2\u2010lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein\u2013coupled 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 (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01 for all). The area under the curve was 0.88 (0.80\u20130.97,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) combining all 4 receptors. Adrenergic \u03b1\n              <jats:sub>1<\/jats:sub>\n              receptor activation associated with OHQ composite score (\u03b2=0.77 OHQ points per SD of activity,\n              <jats:italic>P<\/jats:italic>\n              =0.009) and with reduced tolerability for prolonged standing (\n              <jats:italic>P<\/jats:italic>\n              =0.037) and walking for short (\n              <jats:italic>P<\/jats:italic>\n              =0.042) or long (\n              <jats:italic>P<\/jats:italic>\n              =0.001) periods. All 4 receptors were associated with vision problems (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 for all).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum\u2010mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic \u03b1\n              <jats:sub>1<\/jats:sub>\n              receptor is associated with orthostatic symptoms severity in patients with POTS.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.015989","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T09:11:23Z","timestamp":1596100283000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":51,"title":["Serum Activity Against G Protein\u2013Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome"],"prefix":"10.1161","volume":"9","author":[{"given":"Isabella","family":"Kharraziha","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Internal Medicine Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Axelsson","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Therapy and Apheresis Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Neuroscience, Imaging and Clinical Sciences Institute for Advanced Biomedical Technologies \"G. d'Annunzio\" University Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Martino","sequence":"additional","affiliation":[{"name":"Department of Medicine and Ageing Sciences \"G. d'Annunzio\" University Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaretha","family":"Persson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Internal Medicine Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"National Heart and Lung InstituteImperial CollegeHammersmith Hospital Campus London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Fedorowski","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Cardiology Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Hamrefors","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Internal Medicine Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.1_Part_1.132"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12852"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.03.029"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2018.02.005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203315587566"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000755"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euw154"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.008351"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013602"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00014.2013"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-014-0425-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2018.04.005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-011-0146-2"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2147\/VHRM.S127393"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057109335260"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-014-0981-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.524"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000590050017"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318238bba6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp179"},{"key":"e_1_3_2_22_2","first-page":"439","article-title":"Autonomic control of the eye","volume":"5","author":"McDougal DH","year":"2015","unstructured":"McDougal DH, Gamlin PD. 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