Autoantibody Signature in Cardiac Arrest
Open Access
- 2 June 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American College of Cardiology
- Vol. 141 (22), 1764-1774
- https://doi.org/10.1161/circulationaha.119.044408
Abstract
Background: Cardiac arrest is a tragic event that causes one death roughly every 90 seconds worldwide. Survivors generally undergo a work-up to identify the etiology of arrest. However, 5-10% of cardiac arrest remain unexplained. As cardiac arrhythmias mostly underlie cardiac arrest and increasing evidence strongly supports the involvement of autoantibodies in arrhythmogenesis, a large-panel autoantibody screening was performed in cardiac arrest patients. Methods: This is an observational, cross-sectional study of patients from the Montreal Heart Institute (MHI) hospital cohort, a single center registry of participants. A peptide microarray was designed to screen for IgG targeting epitopes from all known cardiac ion channels with extracellular domains. Plasma samples from 23 patients with unexplained cardiac arrest were compared to 22 cardiac arrest cases of ischemic origin and a group of 29 age-, sex- and BMI-matched healthy subjects. The false discovery rate (FDR), LASSO logistic regression and random forest methods were jointly carried out to find significant differential IgG responses. Results: The autoantibody against the pore domain of the L-type voltage-gated calcium channel (Cav1.2) was consistently identified as a biomarker of idiopathic cardiac arrest (P=0.002, FDR=0.007, classification accuracies ≥0.83). Functional studies on human induced pluripotent stem cell-derived cardiomyocytes demonstrated that the anti-Cav1.2 IgG purified from patients with idiopathic cardiac arrest is proarrhythmogenic by reducing the action potential duration through calcium channel inhibition. Conclusions: The present report addresses the concept of autoimmunity and cardiac arrest. Hitherto unknown autoantibodies targeting extracellular sequences of cardiac ion channels were detected. Moreover, the study identified an autoantibody signature specific to patients with cardiac arrest.This publication has 37 references indexed in Scilit:
- Natural IgG Autoantibodies Are Abundant and Ubiquitous in Human Sera, and Their Number Is Influenced By Age, Gender, and DiseasePLOS ONE, 2013
- SVMTriP: A Method to Predict Antigenic Epitopes Using Support Vector Machine to Integrate Tri-Peptide Similarity and PropensityPLOS ONE, 2012
- Sudden Cardiac Arrest Without Overt Heart DiseaseJournal of the American College of Cardiology, 2011
- Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac deathHeart Rhythm, 2010
- Heart Rate-Dependence of QTc Intervals Assessed by Different Correction Methods in Patients with Normal or Prolonged RepolarizationPacing and Clinical Electrophysiology, 2009
- Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studiesBMJ, 2007
- Assessment of prolonged QT and JT intervals in ventricular conduction defectsThe American Journal of Cardiology, 2004
- Autoimmunity against the second extracellular loop of beta1-adrenergic receptors induces early afterdepolarization and decreases in K-channel density in rabbitsJournal of Invasive Cardiology, 2004
- Screening of Serum Autoantibodies to Cardiac β1-adrenoceptors and M2-muscarinic Acetylcholine Receptors in 408 Healthy Subjects of Varying AgesAutoimmunity, 1999
- A semi‐empirical method for prediction of antigenic determinants on protein antigensFEBS Letters, 1990