In a patient-based study, researchers have found evidence to suggest postural orthostatic tachycardia syndrome (POTS) could be an autoimmune disease. With further investigation, this knowledge could allow for simpler and quicker diagnosis of POTS. The proof-of-concept study is published in the Journal of the American Heart Association.
What is POTS?
POTS is a condition estimated to affect between one and three million people in the United States. Despite its prevalence, its exact cause remains unknown. As the disorder has a similar clinical presentation to many other conditions, it is frequently misdiagnosed.1 Typically characterized by a variety of symptoms, including lightheadedness, so-called ‘brain fog’ and fatigue, POTS tends only to be diagnosed once other conditions have been ruled out. To combat these issues, scientists have been investigating the physiological cause of POTS, with a recent surge of research suggesting it has an autoimmune pathogenesis.
Uncovering a potential cause of POTS
This study used the largest cohort of POTS patients to date, with the researchers hoping to find auto-antibodies against adrenergic and muscarinic receptors in the autonomic nervous system (ANS). These receptors receive signals transmitted by neurons within the ANS, which is responsible for the unconscious control of bodily processes such as maintaining blood pressure, heart rate and breathing rate. Auto-antibodies may lead to the destruction of ANS receptors and thus, if the former were present in a significant amount of the study’s subjects, it could provide an explanation for the symptoms that POTS patients experience.
To determine if this was the case, researchers took blood samples from individuals with POTS. Using ELISA, a technique used to detect proteins, they explored whether autoantibodies to ANS receptors were present in POTS patients.
Their findings show that, out of the 55 subjects, 91% had elevated levels of the nine auto-antibodies being tested for.1 This included those against the adrenergic receptors α1 and 2, β1 and 2 and the five types of muscarinic receptor. These findings were unexpected; William Gunning, Ph.D., told us: “We had expected that adrenergic β2 and muscarinic M4 would be elevated, as these had been reported to be elevated in the literature”, but no previous studies had successfully found elevated levels of all nine auto-antibodies in POTS patients.1
Further surprises were ahead; results showed that the elevation of the remaining eight auto-antibodies was dependent upon elevation of auto-antibodies against adrenergic α1 receptors.
A diagnostic test for POTS?
The positive results of this study raise the question as to whether the findings could be utilized in diagnosing and treating POTS.
Gunning acknowledged that more research would be needed to reach this point. “We plan further studies as we need to do a case-control study as our work was descriptive in nature and we also need to include assays to detect nicotinic and angiotensin receptor autoantibodies. The former was the first autoantibody detected in POTS patients by investigators at the Mayo Clinic and the latter has recently been reported by investigators in Oklahoma City and Sweden.“
“Our results need to be confirmed and once that has been done, detecting elevations of the A1 receptor would indicate this antibody could be used as a laboratory biomarker to help diagnose POTS, which currently is a clinical diagnosis in need of an objective laboratory test.”
Blair Grubb, Ph.D., another of the study’s authors, commented, “For years we have suspected that many patients suffering from postural orthostatic tachycardia syndrome had an autoimmune process at its core. Our paper strongly supports that hypothesis. Not only does is provide insight into the pathogenesis of this (and possibly other related disorders), it also offers the possibility of developing a blood test that can be used in diagnosing patients with postural tachycardia syndrome, much the same way as it is done in diseases such as rheumatoid arthritis.”
“It also opens a potentially whole new realm of treatment possibilities for these patients. We have already begun cautious experiments with using immune-modulating therapy in the sickest patients. Lastly, it is possible that in the future specific monoclonal antibody agents could be developed that treated just the receptors that are affected.”
Grubb cautions that these treatments are not likely to be in the clinic any time soon. “That would be in the far future. So, in a nutshell, it (the study) proves we are right, it has the potential to be a diagnostic modality, and it opens the way for a potentially whole new range of treatment. In short, this could be a game-changer.”
1. Gunning, W.T., et al. (2019) Postural orthostatic tachycardia syndrome is associated with elevated G‐protein coupled receptor autoantibodies. Journal of the American Heart Association. DOI: https://doi.org/10.1161/JAHA.119.013602