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.