title: Autoimmune basis for postural tachycardia syndrome.
abstract: BACKGROUND
  Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR).
  
  
  RESULTS
  Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for α1AR autoantibody-mediated contractility using a perfused rat cremaster arteriole assay. A receptor-transfected cell-based assay was used to detect the presence of β1AR and β2AR autoantibodies. Data were normalized and expressed as a percentage of baseline. The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69±3% compared to 91±1% of baseline for healthy controls, P<0.001) when coexisting β2AR dilative activity was blocked; and this was suppressed by α1AR blockade with prazosin. POTS sera acted as a partial α1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased β1AR activation (130±3% of baseline, P<0.01) and a subset had increased β2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced β1AR and β2AR agonist activity. Autoantibody-positive POTS sera demonstrated specific binding to β1AR, β2AR, and α1AR in transfected cells.
  
  
  CONCLUSIONS
  POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR-mediated tachycardia. Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.
authors.affiliation: Endocrinology and Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center & Veterans Affairs Medical Center, Oklahoma City, OK.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
authors.forename: Xichun
authors.initials: X
authors.lastname: Yu
authors.forename: Campbell
authors.initials: C
authors.lastname: Liles
authors.forename: Muneer
authors.initials: M
authors.lastname: Khan
authors.forename: Megan
authors.initials: M
authors.lastname: Vanderlinde-Wood
authors.forename: Allison
authors.initials: A
authors.lastname: Galloway
authors.forename: Caitlin
authors.initials: C
authors.lastname: Zillner
authors.forename: Alexandria
authors.initials: A
authors.lastname: Benbrook
authors.forename: Sean
authors.initials: S
authors.lastname: Reim
authors.forename: Daniel
authors.initials: D
authors.lastname: Collier
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.forename: Luis E
authors.initials: LE
authors.lastname: Okamoto
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Aston
authors.forename: David C
authors.initials: DC
authors.lastname: Kem
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D015551:Autoimmunity; D001681:Biological Assay; D015415:Biomarkers / Q000097:blood; D016466:CHO Cells; D016022:Case-Control Studies; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009825:Oklahoma; D054972:Postural Orthostatic Tachycardia Syndrome / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D018340:Receptors, Adrenergic, alpha-1 / Q000276:immunology; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology; D018343:Receptors, Adrenergic, beta-2 / Q000276:immunology; D013714:Tennessee; D014162:Transfection; D014661:Vasoconstriction; D014664:Vasodilation; D055815:Young Adult
chemical_list: C547713:ADRA1A protein, human; C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; D000322:Adrenergic Agonists; D001323:Autoantibodies; D015415:Biomarkers; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2
keywords: adrenergic receptor; autoantibody; autonomic function; postural tachycardia syndrome