# Autoimmune Basis for Postural Tachycardia Syndrome

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 · $490,391

## Abstract

Project Summary
Postural tachycardia syndrome (POTS) is a debilitating disorder resulting from cardiovascular autonomic
dysfunction, has many causes and is very difficult to treat effectively. This renewal proposal builds on the
work that supports a pathophysiological role for functional adrenergic autoantibodies in POTS. The
differing allosteric effects of these antibodies on the natural ligands provide an explanation for increased
sympathetic activity and exaggerated orthostatic tachycardia characteristic of POTS. However, the
mechanism for decreased parasympathetic activity in POTS patients is yet to be elucidated. This
proposal tests the hypothesis that muscarinic autoantibody-mediated parasympathetic dysfunction
contributes to the pathogenesis of POTS, and that parasympathetic (vagal) stimulation improves POTS
symptoms, autoimmunity and inflammation. The long-term goal is to evaluate the significance of
autoimmune-mediated sympathovagal imbalance in the pathophysiology of POTS and to establish
transcutaneous vagus nerve stimulation (tVNS) as a safe and effective treatment option for POTS. The
specific aims are to: 1) determine the prevalence, burden, and clinical significance of muscarinic
autoantibodies in a well-phenotyped cohort of POTS patients and a matched cohort of healthy control
subjects; 2) examine the in vivo impact of muscarinic autoantibodies on cardiovagal activity in a rabbit
autoimmune model developed during the current funding period; and 3) investigate the potential
therapeutic mechanisms of tVNS in POTS patients and in animal model. tVNS is an important treatment
modality that needs to cross the translational bridge between basic science and clinical research.
Findings from these studies will provide realistic expectation of new knowledge regarding the etiology of
this disabling disorder and lay the foundation for a paradigm shift for the treatment of POTS.

## Key facts

- **NIH application ID:** 10405660
- **Project number:** 5R01HL128393-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Xichun Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $490,391
- **Award type:** 5
- **Project period:** 2015-09-04 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405660

## Citation

> US National Institutes of Health, RePORTER application 10405660, Autoimmune Basis for Postural Tachycardia Syndrome (5R01HL128393-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10405660. Licensed CC0.

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