Abstract
Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular autonomic disorder characterized by orthostatic intolerance and high prevalence among young women. The etiology of POTS is uncertain, though autoimmunity and inflammation may play an important role. We aimed to identify novel inflammatory biomarkers associated with POTS.Methods and Results: In the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort, we identified 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal haemodynamic response during passive head-up-tilt test (n = 283). Blood samples were analyzed using antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. POTS patients were younger (26 vs. 31 years; p < 0.001) and there was no significant difference in sex distribution (74% vs. 67% females, p = 0.24). PCA and Bonferroni-adjusted ANOVA identified proconvertase furin as the most robust biomarker signature for POTS. Plasma level of proconvertase furin was lower (6.38 vs. 6.58 of normalized protein expression units (NPX); p < 0.001 in POTS, compared with the reference group. Proconvertase furin met Bonferroni-adjusted significance criteria in both uni- and multivariable regression analyses.Conclusion: Patients with POTS have lower plasma level of proconvertase furin compared with individuals with normal postural hemodynamic response. This finding suggests the presence of a specific autoimmune trait with disruption of immune peripheral tolerance in this hitherto unexplained condition. Further studies are needed for external validation of our results.
Highlights
Postural orthostatic tachycardia syndrome (POTS) is a complex condition featuring signs of autonomic dysfunction with both cardiovascular and non-cardiovascular symptoms (Benarroch, 2012)
It has already been established that activating autoantibodies (AAb) to the α1-adrenergic (α1AR), β1/2-adrenergic receptors (β1/2AR), and angiotensin-receptor type 1 can be found in serum from POTS patients but not in controls (Fedorowski et al, 2017; Yu et al, 2018)
The dataset consisted of 396 patients (113 POTS and 283 controls)
Summary
Postural orthostatic tachycardia syndrome (POTS) is a complex condition featuring signs of autonomic dysfunction with both cardiovascular and non-cardiovascular symptoms (Benarroch, 2012). It has been observed that some patients develop POTS after experiencing a febrile illness, presumably viral (Grubb, 2008; Li et al, 2014). This has led to the hypothesis of an autoimmune-mediated etiology of POTS, and recent case series of POTS following immune triggers like infection or vaccination (Blitshteyn, 2015; Brinth et al, 2015; Watari et al, 2018) support this hypothesis. In current knowledge of the presence of autoantibodies and possible immunological triggers, exploration of expression of inflammatory mediators in POTS is required, both as a potential diagnostic tool and therapeutic target in this ill-understood condition for which there is no effective treatment. We aimed to identify novel inflammatory biomarkers associated with POTS
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