{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:41:40Z","timestamp":1784324500472,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (\u03b4-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\u2013control 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 \u201cnon-POTS\u201d 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 &lt; 0.0001. Of particular interest were elevations of IL-1\u03b2 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 \u03b4-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.<\/jats:p>","DOI":"10.3390\/cells11050774","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T09:34:38Z","timestamp":1645608878000},"page":"774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4190-2479","authenticated-orcid":false,"given":"William T.","family":"Gunning","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Cichocki","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly L.","family":"Karabin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadik A.","family":"Khuder","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3308-2156","authenticated-orcid":false,"given":"Blair P.","family":"Grubb","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102828","DOI":"10.1016\/j.autneu.2021.102828","article-title":"Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting\u2014Part 1","volume":"235","author":"Vernino","year":"2021","journal-title":"Auton. 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