Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome

Yu, Xichun; Li, Hongliang; Murphy, Taylor A.; Nuss, Zachary; Liles, Jonathan; Liles, Campbell; Aston, Christopher E.; Raj, Satish R.; Fedorowski, Artur; Kem, David C.

doi:10.1161/jaha.117.008351

Cited by 70 publications

(51 citation statements)

References 24 publications

(52 reference statements)

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“…5 These findings would fit with the fact that autoantibodies to autonomic receptors have been found in affected patients, although actual causation has not been established. [10][11][12][13] We also found that just over half of our patients had some aspect of joint hypermobility, with either hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorder. 5 This also has been borne out in other studies, [14][15][16] suggesting a strong association with this disorder, as well.…”

Section: Discussionsupporting

confidence: 62%

Family history of associated disorders in patients with postural tachycardia syndrome

Boris¹,

Huang

Shuey³

et al. 2020

Cardiol Young

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Introduction:Postural tachycardia syndrome is more frequently being recognised in adolescents and adults. However, its pathophysiology remains undefined. We evaluated our database for patterns in family history of clinical symptoms and associated disorders in these patients.Materials and methods:Patients with postural tachycardia syndrome diagnosed in our clinic between 2014 and 2018 and who were less than 19 years at diagnosis were included. The history was reviewed for family members with postural tachycardia syndrome, dizziness and/or syncope, joint hypermobility with or without hypermobile Ehlers–Danlos syndrome, and autoimmune disorders. Statistical analysis assessed the entire cohort plus differences in gender, presence or absence of joint hypermobility, and presence or absence of familial autoimmune disease.Results:A total of 579 patients met inclusion criteria. We found that 14.2% of patients had a family member with postural tachycardia syndrome, with male patients more likely to have an affected family member (20% versus 12.7%, p = 0.04). If the patient also had joint hypermobility, male patients were more likely to have a family member with postural tachycardia syndrome (25% versus 12.6%, p = 0.017), more than one affected family member (7.1% versus 0.74%, p = 0.001), and a family member with joint hypermobility (37.5% versus 23.7%, p = 0.032). Autoimmune disease was seen in 45.1% of family members, but more likely in female patients with concurrent hypermobility (21.1% versus 8.9%, p = 0.035).Discussion:This in-depth analysis of associated familial disorders in patients with postural tachycardia syndrome offers further insight into the pathophysiology of the disorder, and informs further screening of family members in these patients.

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Section: Discussionsupporting

confidence: 62%

Family history of associated disorders in patients with postural tachycardia syndrome

Boris¹,

Huang

Shuey³

et al. 2020

Cardiol Young

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“…In recent years, search for the presence of a hypothetical immunological fingerprint in POTS has resulted in a discovery of diverse autoantibodies with a proposed causative role in the syndrome . A specific focus was given cardiovascular G‐protein‐coupled membrane complexes, such as adrenergic, muscarinic and angiotensin II type‐1 receptors The symptoms of POTS, especially tachycardia, could be evoked by the direct action on sinus rate controlling system (via adrenergic and muscarinic receptors) or through a compensatory mechanism responding to peripheral vasodilation (via adrenergic, angiotensin and other possible vasoactive receptors) (Fig.…”

Section: The Aetiology Of Potsmentioning

confidence: 99%

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management

2018

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Fedorowski A (Malm€ o Lund University; Sk ane University Hospital, Malm€ o, Sweden). Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (Review). J Intern Med 2019; 285: 352-366.Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affects younger individuals 15-45 years old with a distinct female predominance (%80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, 'brain fog', dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring. Although long-term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1-3 years. After the diagnosis has been established, patient should be thoroughly educated about non-pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.

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“…This study points the way toward application of other proteomics technology in POTS research. For instance, it might be useful to use similar technology to screen a large number of antibody variable region epitope sequences for coexisting antibodies that might be directed toward candidate G-protein coupled receptors considered relevant to POTS [3,45] and related conditions such as chronic fatigue syndrome.…”

Section: Final Remarksmentioning

confidence: 99%

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome

Spahic

Ricci

Aung

et al. 2020

BMC Cardiovasc Disord

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Background: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology. Methods: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction. Results: POTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS. Conclusions: Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

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Angiotensin II Type 1 Receptor Autoantibodies in Postural Tachycardia Syndrome

Cited by 70 publications

References 24 publications

Family history of associated disorders in patients with postural tachycardia syndrome

Family history of associated disorders in patients with postural tachycardia syndrome

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome

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