Autoantibody Signature in Cardiac Arrest

<p><strong>Background:</strong> Cardiac arrest is a tragic event that causes one death roughly every 90 seconds</p> <p>worldwide. Survivors generally undergo a work-up to identify the etiology of arrest. However, 5-</p> <p>10% of cardiac arrest remain unexplained. As cardiac arrhythmias mostly underlie cardiac arrest</p> <p>and increasing evidence strongly supports the involvement of autoantibodies in</p> <p>arrhythmogenesis, a large-panel autoantibody screening was performed in cardiac arrest patients.</p> <p><strong>Methods:</strong> This is an observational, cross-sectional study of patients from the Montreal Heart</p> <p>Institute (MHI) hospital cohort, a single center registry of participants. A peptide microarray was</p> <p>designed to screen for IgG targeting epitopes from all known cardiac ion channels with</p> <p>extracellular domains. Plasma samples from 23 patients with unexplained cardiac arrest were</p> <p>compared to 22 cardiac arrest cases of ischemic origin and a group of 29 age-, sex- and BMImatched</p> <p>healthy subjects. The false discovery rate (FDR), LASSO logistic regression and</p> <p>random forest methods were jointly carried out to find significant differential IgG responses.</p> <p><strong>Results: </strong>The autoantibody against the pore domain of the L-type voltage-gated calcium channel</p> <p>(Cav1.2) was consistently identified as a biomarker of idiopathic cardiac arrest (P=0.002,</p> <p>FDR=0.007, classification accuracies &ge;0.83). Functional studies on human induced pluripotent</p> <p>stem cell-derived cardiomyocytes demonstrated that the anti-Cav1.2 IgG purified from patients</p> <p>with idiopathic cardiac arrest is proarrhythmogenic by reducing the action potential duration</p> <p>through calcium channel inhibition.</p> <p><strong>Conclusions: </strong>The present report addresses the concept of autoimmunity and cardiac arrest.</p> <p>Hitherto unknown autoantibodies targeting extracellular sequences of cardiac ion channels were</p> <p>detected. Moreover, the study identified an autoantibody signature specific to patients with</p> <p>cardiac arrest.</p>