10.3389/fnins.2019.00301.s001
Jasmina Medic Spahic
Jasmina Medic
Spahic
Fabrizio Ricci
Fabrizio
Ricci
Nay Aung
Nay
Aung
Jonas Axelsson
Jonas
Axelsson
Olle Melander
Olle
Melander
Richard Sutton
Richard
Sutton
Viktor Hamrefors
Viktor
Hamrefors
Artur Fedorowski
Artur
Fedorowski
Image_1_Proconvertase Furin Is Downregulated in Postural Orthostatic Tachycardia Syndrome.JPEG
Frontiers
2019
postural orthostatic tachycardia syndrome
inflammation
biomarkers
proteomics
proconvertase furin
2019-03-29 13:09:19
Figure
https://frontiersin.figshare.com/articles/figure/Image_1_Proconvertase_Furin_Is_Downregulated_in_Postural_Orthostatic_Tachycardia_Syndrome_JPEG/7924619
<p>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.</p><p>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.</p><p>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.</p>