Recurrent Myocarditis in Patients With Desmosomal Pathogenic Variants: Is Self Antigen Presentation the Link?

Myocarditis is frequently associated with viral infections. Increasing evidence points to an association between myocarditis and inherited cardiomyopathies, though it is unclear whether myocarditis is a driver or an accessory. We present a primary vignette and case series highlighting recurrent myocarditis in patients later found to harbor pathogenic desmosomal variants and provide clinical and basic science context, exploring 2 potentially overlapping hypotheses: that stress induces cellular injury and death in structurally abnormal myocytes and that recurrent viral myocardial and truncated desomosomal protein byproducts as 2 hits could lead to loss of immune tolerance and subsequent autoreactivity.
Competing Interests: Funding Support and Author Disclosures Dr Sheikh is a cofounder and has equity interest in Papillon Therapeutics Inc; is a consultant and has equity interest in LEXEO Therapeutics Inc; and was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL142251; HL162369), Department of Defense (W81XWH1810380), and LEXEO Therapeutics Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)