Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome

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.

Investigating the possible mechanisms of autonomic dysfunction post-COVID-19

“…A link between autoinflammation and autoimmunity is represented by the mixed pattern disease ( Rodríguez et al, 2020 ). Evidence has recently shown that POTS may in fact be a mixed pattern inflammatory disease mediated by T cells ( Gunning et al, 2022 ). This was based on a study that showed a platelet delta granule storage pool deficiency in patients with POTS and GPCR autoantibodies suggesting innate system activation ( Gunning et al, 2021 ; Gunning et al, 2022 ).…”

“…Evidence has recently shown that POTS may in fact be a mixed pattern inflammatory disease mediated by T cells ( Gunning et al, 2022 ). This was based on a study that showed a platelet delta granule storage pool deficiency in patients with POTS and GPCR autoantibodies suggesting innate system activation ( Gunning et al, 2021 ; Gunning et al, 2022 ). It remains to be investigated whether the innate and adaptive immune systems contribute to autoantibody production against adrenergic and cholinergic receptors following SARS-CoV-2 infection.…”

Modifying Orthobiological PRP Therapies Are Imperative for the Advancement of Treatment Outcomes in Musculoskeletal Pathologies

“…The ill-defined grey bodies represent the α-granules, approximately 50–80/platelet. The opaque round bodies are the dense granules, ranging from 0–30/platelet, and grey string-like bodies are lysosomes [ 24 ]. Thin lines signify platelet cell membranes.…”

Post-COVID-19 postural orthostatic tachycardia syndrome

“…The mechanism of POTS is unknown, although research is continuing to find the most likely reasons. People with POTS have platelet storage pool shortage, according to Gunning et al [ 9 ], which is connected to symptoms including nosebleeds, dysmenorrhea, easy bruising, and anemia. It was also shown that persons with POTS have higher inflammatory biomarkers, all of which might indicate a chronic inflammatory condition.…”

“…It was also shown that persons with POTS have higher inflammatory biomarkers, all of which might indicate a chronic inflammatory condition. The presented conditions, especially inflammatory markers, could be associated with a cytokine storm during COVID-19 [ 9 ]. POTS affected an estimated 1–3 million persons in the United States, well before the pandemic, according to data published by the group Dysautonomia International.…”