Autoimmune basis for postural tachycardia syndrome

Area of Science:

• Cardiology
• Immunology
• Neuroscience

Background:

• Postural tachycardia syndrome (POTS) is characterized by exaggerated orthostatic tachycardia, often post-viral, suggesting an autoimmune basis.
• Autoimmunity is hypothesized to play a key role in POTS pathophysiology.
• This study investigated functional autoantibodies against adrenergic receptors (AR) in POTS patients.

Purpose of the Study:

• To test the hypothesis that POTS patients harbor functional autoantibodies to adrenergic receptors (AR).
• To investigate the role of autoantibodies in the pathophysiology of POTS.
• To identify specific adrenergic receptor targets of autoantibodies in POTS.

Main Methods:

• Examined α1AR autoantibody-mediated contractility using a perfused rat cremaster arteriole assay in 14 POTS patients and 10 healthy controls.
• Utilized a receptor-transfected cell-based assay to detect β1AR and β2AR autoantibodies.
• Analyzed autoantibody binding to α1AR, β1AR, and β2AR in transfected cells.

Main Results:

• POTS patient sera showed significant arteriolar contractile activity mediated by α1AR autoantibodies, suppressed by prazosin.
• POTS sera acted as a partial α1AR antagonist, shifting phenylephrine curves.
• All POTS sera increased β1AR activation, with a subset showing increased β2AR activity, consistent with enhanced agonist activity and specific autoantibody binding.

Conclusions:

• POTS patients exhibit elevated α1AR autoantibodies causing a partial peripheral antagonist effect.
• Compensatory sympathoneural activation of α1AR and concurrent βAR-mediated tachycardia contribute to POTS symptoms.
• Coexisting β1AR and β2AR agonistic autoantibodies likely facilitate tachycardia, explaining increased plasma norepinephrine and excessive heart rate in POTS.