Inflammatory Biomarkers in Postural Orthostatic Tachycardia Syndrome with Elevated G-Protein-Coupled Receptor Autoantibodies.

William T Gunning,Stanislaw M Stepkowski,Beverly L Karabin,Paula M Kramer,Blair P Grubb

doi:10.3390/jcm10040623

Abstract

A growing body of evidence suggests that postural orthostatic tachycardia syndrome (POTS) may be an autoimmune disorder. We have reported in a previous manuscript that 89% of POTS patients (n = 55) had elevations in G-protein-coupled adrenergic A1 receptor autoantibodies and 53% had elevations in muscarinic acetylcholine M4 receptor autoantibodies, as assessed by ELISA. Patients with autoimmune disorders have been reported with a variety of elevated cytokines and cytokines (such as rheumatoid arthritis); thus, we evaluated a limited number of cytokines/chemokines in POTS patients with elevated adrenergic and muscarinic receptor autoantibodies. We utilized the plasma of 34 patients from a previous study; all of the patients (100%) had autoantibodies against the A1 adrenergic receptor and 55.9% (19/34) had autoantibodies against the M4 muscarinic acetylcholine receptor. In particular, the plasma cytokine/chemokine levels were measured as biomarkers of inflammation by Quantibody® technology (Raybiotech, Peachtree Corners, GA, USA). We also evaluated the platelet dense granule numbers, as these patients frequently complain of symptoms related to platelet dysfunction. Patients were predominantly young females who displayed a multitude of co-morbidities but generally reported viral-like symptoms preceding episodes of syncope. Eighty five percent (29/34) had platelet storage pool deficiency. Patients had elevations in five of ten cytokine/chemokines biomarkers (IL1β, IL21, TNFα, INFγ, and CD30), whereas two biomarkers had decreased levels (CD40L and RANTES). Our observations demonstrate that POTS patients known to have autoantibodies against the G-protein-coupled adrenergic A1 receptor have abnormal plasma concentrations of inflammatory cytokines.

Highlights

There is a growing body of evidence suggesting that postural orthostatic tachycardia syndrome (POTS) might be an autoimmune disease
Could the δ-SPD we have found in a majority of POTS patients be acquired due to an autoimmune process? Could the platelet play a role in potential autoimmunity in POTS? Is this related to an innate immune system activation?
We have previously reported that many POTS patients report symptoms of easy bruising and frequent nosebleeds, and, for women, heavy menstrual bleeding [7]

Summary

Introduction

There is a growing body of evidence suggesting that postural orthostatic tachycardia syndrome (POTS) might be an autoimmune disease. Postural orthostatic tachycardia syndrome affects as many as 3 million people in the United States [3], predominantly young women of child bearing age [4,5]. Common clinical symptoms identified in affected patients include light-headedness, dizziness, and fainting episodes;. A racing heart; chest pain; abdominal pain and/or nausea; sleep problems; headaches; and cognitive issues. Many of these symptoms are confounders, implicating a variety of potential etiologies of POTS [6,7,8]. A general consensus for the diagnosis of the disorder requires the presence of chronic orthostatic intolerance associated with an increased heart rate of ≥30 beats per minute (BPM) from the supine or sitting basal rate or a rate that exceeds 120 BPM when standing or by an upright tilt test that occurs within 10 min [9,10]

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