Reply to the Editor— POTS: A neuroimmune disorder with cardiovascular manifestations

We would like to thank Blitshteyn for taking the time to read our article 1 and provide their comments.Although our study 1 lacked a healthy control group, a previous study 2 from our lab included 19 healthy controls and demonstrated that ST-segment depression in response to elevated sympathetic tone, measured by skin sympathetic nerve activity (SKNA).That finding is consistent with the current study's results.The clinical implications of our study would be further strengthened if we could determine the relationship between ST height and average SKNA in patients with J-wave syndrome, which is associated with nocturnal ST elevation, ventricular arrhythmias, and sudden death.Blitshteyn et al. 3 present possible mechanistic explanations for this phenomenon, including small-fiber neuropathy (SFN), brain and brainstem abnormalities, and immunologic and autoimmune perturbations.Interestingly, they also propose the classification of POTS as a neuroimmune disorder. 4Their suggestion that the pathophysiology of POTS has a neuroimmune etiology with downstream effects on cardiovascular regulation has merit, given the multisystemic manifestations of the disorder.We also appreciate that they mention studies demonstrating central nervous system disorders, such as alterations in the glymphatic system, in POTS. 4,5The glymphatic system is a perivascular cerebrospinal fluid (CSF) -interstitial fluid exchange pathway that supports brain homeostasis by clearing cellular debris and soluble antigens. 6ymphatic system dysfunction is commonly observed in central nervous system diseases 7 while CSF production is subjected to autonomic control. 8It is possible that patients with dysautonomia, such as POTS, may suffer from glymphatic system dysfunction, which aggravates the symptoms.More work in this area may help develop novel therapies for POTS.We thank Blitshteyn for providing these insightful comments.