Abstract
A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease. In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated. This case–control study validates our pilot study results that POTS patients have an activated innate immune system. Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as “non-POTS” subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules. Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001. Of particular interest were elevations of IL-1β and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory. All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.
Highlights
Postural orthostatic tachycardia syndrome (POTS) is a condition of orthostatic intolerance with a racing heart and a multitude of symptoms, induced upon standing and relieved when becoming supine [1]
We have empirical evidence that the acquired δ-SPD may be related to viral infection and/or chronic inflammation and, based upon this, we explored a number of cytokines and chemokines related to platelet activation in a limited number of POTS patients that had elevations of G-protein-linked autoantibodies against the alpha 1 adrenergic receptor [11]
POTS patients were found to have a mean of 2.65 ± 0.22 DG/PL, which is consistent with δ-SPD, in contrast to non-POTS subjects, who had normal numbers of DGs (4.95 ± 0.11 DG/PL) (p < 0.0001)
Summary
Postural orthostatic tachycardia syndrome (POTS) is a condition of orthostatic intolerance with a racing heart and a multitude of symptoms, induced upon standing and relieved when becoming supine [1]. Common nonspecific symptoms reported with POTS include exercise intolerance, fatigue, lightheadedness, palpitations, nausea, headache, diminished concentration (“brain fog”), near syncope, and syncope. It is a debilitating disorder, affecting an estimated 1% of the population and likely more with the numerous reports in the literature of COVID-19 “long haulers” exhibiting many of the symptoms described by POTS patients; a number of these patients have been diagnosed with POTS [2,3,4,5,6]. There is a growing body of evidence suggesting that POTS is an autoimmune disease [13,14,15,16,17,18]
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