Study identifies first potential biomarker for a debilitating fainting condition

Summary: Postural orthostatic tachycardia syndrome (POTS), a disorder characterized by sudden fainting, may be an autoimmune disease. A new study reveals 89% of patients with the condition had elevated levels of autoantibodies against the adrenergic alpha 1 receptor. The potential biomarker can be identified via blood samples.

Source: University of Toledo

New research from The University of Toledo College of Medicine and Life Sciences strongly suggests postural orthostatic tachycardia syndrome, or POTS, is an autoimmune disorder and may help pave the way for a simple blood test that could help physicians diagnose the condition.

POTS is characterized by large increases in heart rate and sometimes decreases in blood pressure when standing up. That can cause lightheadedness, heart palpitations and even loss of consciousness. In addition to fainting, POTS patients also regularly suffer from a litany of additional symptoms, including fatigue, pain, gastrointestinal issues, bleeding disorders, anxiety and brain fog.

About 3 million Americans are believed to be affected, but because of its wide-ranging and seemingly unrelated symptoms, POTS is notoriously difficult to identify.

“The trouble with diagnosing POTS is that it’s currently principally a clinical diagnosis. It’s based on history, the absence of other illness as well as the finding of increase in heart rate when standing. There is no blood test right now to aid in the diagnosis. It can be an incredibly frustrating process for patients,” said Dr. Blair Grubb, Distinguished University Professor of Medicine and Pediatrics in the UToledo College of Medicine and Life Sciences and director of electrophysiology services at The University of Toledo Medical Center.

In the largest study of POTS patients to date, published Sept. 9 in the Journal of the American Heart Association, Grubb and UToledo research collaborators found 89 percent of patients they examined had elevated levels of autoantibodies against the adrenergic alpha 1 receptor.

“People have suspected an autoimmune connection for years, and other small-scale studies have suggested it,” said Grubb, one of the world’s foremost experts in syncope and disorders of the autonomic nervous system. “We did a much larger cross-section of patients than has ever been done before, and found that almost all of them tested positive for autoimmune antibodies. That’s a significant finding.”

None of the 55 patients who participated in the study had another recognized autoimmune disorder. Fifty-two were female, with an average age of 30.

Researchers screened the patients’ blood for autoantibodies against nine receptors. A handful of patients showed elevated levels against all nine. But it was the prevalence of adrenergic A1 subtype receptor autoantibodies that make their findings so intriguing.

“I think that we have identified a biomarker. We now might have the ability to diagnosis this, or at least have an inkling. Like other autoimmune diseases, we can take a blood sample and detect if there are increased levels of autoantibodies present. According to our results, autoantibodies against this particular receptor should be present in about 90 percent of patients with POTS,” said Dr. William Gunning, a professor of pathology in the UToledo College of Medicine and Life Sciences, and the paper’s lead author.

This shows a young woman laying on the floor
However, this study adds significantly to the evidence that POTS is an autoimmune disorder. The image is in the public domain.

Gunning and Grubb say much more research is needed. However, this study adds significantly to the evidence that POTS is an autoimmune disorder — and it shows it may be possible to give physicians unfamiliar with the condition an easy way to test for it.

“What this does is prove the concept,” Grubb said. “Other studies had used very expensive research tests. What we used are the same kind of testing methods that would be used by regular hospitals. We wanted to do something that would potentially be a test applicable to the general population, not just a research test.”

While Gunning and Grubb caution they’re still investigating the precise methods by which POTS is established, their study does raise the possibility that existing immune modulating medications could be a viable therapeutic method for some patients.

Funding: The study was supported by funding from the Dysautonomia Advocacy Foundation, the Life as a Zebra Foundation, and the Virginia Lounsbury Foundation.

About this neuroscience research article

University of Toledo
Media Contacts:
Tyrel Linkhorn – University of Toledo
Image Source:
The image is in the public domain.

Original Research: Open access
“Postural Orthostatic Tachycardia Syndrome Is Associated With Elevated G‐Protein Coupled Receptor Autoantibodies”. William T. GunningIII, Heather Kvale, Paula M. Kramer, Beverly L. Karabin, and Blair P. Grubb.
JAHA: Journal of the American Heart Association doi:10.1161/JAHA.119.013602


Postural Orthostatic Tachycardia Syndrome Is Associated With Elevated G‐Protein Coupled Receptor Autoantibodies

The etiology of postural orthostatic tachycardia syndrome (POTS) is yet to be established. The disorder is often misdiagnosed as chronic anxiety or a panic disorder because the autonomic failure in these patients is not severe. A growing body of evidence suggests that POTS may be an autoimmune disorder. Antinuclear antibodies and elevations of ganglionic, adrenergic, and muscarinic acetylcholine receptor antibodies have all been reported.

Methods and Results
We collected detailed clinical symptoms of 55 patients diagnosed with POTS. We also evaluated serum levels of autoantibodies against 4 subtypes of G‐protein coupled adrenergic receptors and 5 subtypes of G‐protein coupled muscarinic acetylcholine receptors by ELISA. Our patients had a multitude of comorbidities, were predominantly young females, and reported viral‐like symptoms preceding episodes of syncope. We detected a significant number of patients with elevated levels of autoantibodies against the adrenergic alpha 1 receptor (89%) and against the muscarinic acetylcholine M4 receptor (53%). Surprisingly, elevations of muscarinic receptor autoantibodies appeared to be dependent upon elevation of autoantibodies against the A1 adrenergic receptor! Four patients had elevations of G‐protein coupled autoantibodies against all 9 receptor subtypes measured in our study. Five POTS patients had no elevation of any autoantibody; similarly, controls were also negative for autoantibody elevations. There was a weak correlation of clinical symptom severity with G‐protein coupled autoantibodies.

Our observations provide further evidence that, in most cases, POTS patients have at least 1 elevated G‐protein coupled adrenergic autoantibody and, in some instances, both adrenergic and muscarinic autoantibodies, supporting the hypothesis that POTS may be an autoimmune disorder.

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