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Antiadrenergic autoimmunity in postural tachycardia syndrome

Fedorowski, Artur LU ; Li, Hongliang; Yu, Xichun; Koelsch, Kristi A.; Harris, Valerie M.; Liles, Campbell; Murphy, Taylor A.; Quadri, Syed M.S.; Scofield, Robert Hal and Sutton, Richard, et al. (2017) In Europace 19(7). p.1211-1219
Abstract

Aims 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). Methods and 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... (More)

Aims 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). Methods and 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. Conclusion 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.

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published
subject
keywords
Adrenergic receptors, Allosteric activation, Autoimmunity, Postural tachycardia syndrome, Vasovagal syncope
in
Europace
volume
19
issue
7
pages
9 pages
publisher
Oxford University Press
external identifiers
  • scopus:85026405850
  • wos:000405582500026
ISSN
1099-5129
DOI
10.1093/europace/euw154
language
English
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yes
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3087d5cf-8829-4cad-ad45-822f927b86eb
date added to LUP
2017-08-25 14:21:24
date last changed
2017-09-18 11:43:14
@article{3087d5cf-8829-4cad-ad45-822f927b86eb,
  abstract     = {<p>Aims 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). Methods and 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. Conclusion 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.</p>},
  author       = {Fedorowski, Artur and Li, Hongliang and Yu, Xichun and Koelsch, Kristi A. and Harris, Valerie M. and Liles, Campbell and Murphy, Taylor A. and Quadri, Syed M.S. and Scofield, Robert Hal and Sutton, Richard and Melander, Olle and Kem, David C.},
  issn         = {1099-5129},
  keyword      = {Adrenergic receptors,Allosteric activation,Autoimmunity,Postural tachycardia syndrome,Vasovagal syncope},
  language     = {eng},
  month        = {07},
  number       = {7},
  pages        = {1211--1219},
  publisher    = {Oxford University Press},
  series       = {Europace},
  title        = {Antiadrenergic autoimmunity in postural tachycardia syndrome},
  url          = {http://dx.doi.org/10.1093/europace/euw154},
  volume       = {19},
  year         = {2017},
}