title: Antiadrenergic autoimmunity in postural tachycardia syndrome.
abstract: OBJECTIVE
  Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR).
  
  
  RESULTS
  Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.
  
  
  CONCLUSIONS
  These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.|Department of Cardiology, Skåne University Hospital, Inga Marie Nilssons gata 46, Malmö 20502, Sweden.
authors.forename: Artur
authors.initials: A
authors.lastname: Fedorowski
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Xichun
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.|Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Koelsch
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.|Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Harris
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Campbell
authors.initials: C
authors.lastname: Liles
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Murphy
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.|Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Syed M S
authors.initials: SMS
authors.lastname: Quadri
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.|Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Robert Hal
authors.initials: RH
authors.lastname: Scofield
authors.affiliation: National Heart & Lung Institute, Imperial College, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, OK, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Kem
mesh_terms: D000009:Abdominal Muscles / Q000098:blood supply*; D000293:Adolescent; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D016466:CHO Cells; D016022:Case-Control Studies; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D066298:In Vitro Techniques; D008297:Male; D054972:Postural Orthostatic Tachycardia Syndrome / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014661:Vasoconstriction / Q000187:drug effects; D055815:Young Adult
chemical_list: C547713:ADRA1A protein, human; C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; D058646:Adrenergic alpha-1 Receptor Agonists; D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D001323:Autoantibodies; D007074:Immunoglobulin G; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2
keywords: Adrenergic receptors; Allosteric activation; Autoimmunity; Postural tachycardia syndrome; Vasovagal syncope