Role of Anti-TREK-1 Autoantibodies in SCVF

Condition(s) studied

Investigational drug(s) / intervention(s)

Repeat plasma screening for the presence or absence of anti-TREK-1 autoantibodies: Semiquantitative measure of circulating anti-TREK-1 autoantibodies in plasma of study participants using a peptid microarray

DPP6 risk haplotype: Systematic genetic screening for the Dutch DPP6 risk haplotype in all study participants and correlation of results with the presence or absence of anti-TREK-1 autoantibodies

Study summary

Short-coupled ventricular fibrillation (SCVF) is a lethal, primary electrical disorder and an important cause of unexplained cardiac arrest.1 Recent work from our group suggests that a substantial proportion of SCVF cases is associated to circulating autoantibodies targeting TREK-1, a cardiac potassium channel, resulting in an abnormal gain-of-function which is the prerequisite for the SCVF phenotype.2 This proposal is a translational multicenter study to validate anti-TREK-1 autoantibodies as a diagnostic and prognostic biomarker in a large, diversified cohort of SCVF patients (Figure 1). Functional, cellular experiments in patient-derived hiPSC cardiomyocytes and Purkinje cells will be performed to explore the cell type-specific role of TREK-1 in arrhythmogenesis, while single-nuclear RNA sequencing (snRNA-seq) will allow us to establish the transcriptomic profile (Figure 1). These results will identify the cellular substrate for SCVF.

Eligibility

Primary outcome measure(s)

• Presence of anti-TREK-1 autoantibodies at three different time points — 12 months
  Plasma concentrations of anti-TREK-1 autoantibodies (semiquantitative measure using a peptide microarray at three predefined time points

Trial sites (5)

More Institut universitaire de cardiologie et de pneumologie de Québec, University Laval trials in Canada