Detection of G Protein–Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology

Abstract

Background: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein–coupled receptors between patients with POTS and healthy controls. Methods: Sera were collected from 116 patients with POTS (91% female; medium age, 29 years) and 81 healthy controls (84% female; medium age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay. Results: Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls. Conclusions: Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay–derived autoantibody concentrations to cardiovascular G protein–coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.

Orexin/hypocretin system dysfunction in patients with Takotsubo syndrome: A novel pathophysiological explanation

“…One recent study aimed to measure G protein-coupled receptor autoantibodies in POTS. However, results from this study could not prove that patients with POTS and healthy controls had different autoantibody concentrations for several cardiovascular GPCRs ( 80 ). Autoimmunity has been suggested to play a potential role in the underlying pathophysiology of both POTS and TTS ( 80 , 81 ).…”

“…However, results from this study could not prove that patients with POTS and healthy controls had different autoantibody concentrations for several cardiovascular GPCRs ( 80 ). Autoimmunity has been suggested to play a potential role in the underlying pathophysiology of both POTS and TTS ( 80 , 81 ). With that in mind, and in the context of orexin-system dysfunction, future studies should assess orexin autoantibodies in both TTS and POTS.…”

Impact of the COVID‐19 pandemic on clinical autonomic practice in Europe: a survey of the European Academy of Neurology and the European Federation of Autonomic Societies

“…Antibodies against G‐protein‐coupled cardiovascular receptors have been formerly hypothesized to contribute to POTS pathogenesis [32, 33]. However, more recent studies found positive antibody titers against G‐protein‐coupled cardiovascular receptors also in healthy people [34], questioning their pathogenic role in POTS settings. Interestingly, autoimmune autonomic ganglionopathy, an autonomic disorder mediated by antibodies against the α 3 ‐subunit of the ganglionic nicotinic acetylcholine receptor, was only rarely diagnosed after COVID‐19 infection by the survey responders.…”

“…Antibodies against G-protein-coupled cardiovascular receptors have been formerly hypothesized to contribute to POTS pathogenesis [32,33]. However, more recent studies found positive antibody titers against G-protein-coupled cardiovascular receptors also in healthy people [34], questioning their pathogenic role in POTS settings.…”

Estudio y manejo de las neuropatías de fibra fina

“…Es especialmente frecuente el anticuerpo contra el receptor alfa-1 adrenérgico, seguido del muscarínico M4 67 . Sin embargo, la especificad de detección de estos anticuerpos por medios convencionales (ELISA) está en entredicho debido a la frecuencia de falsos positivos en pacientes controles 68 .…”