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

Jacob J Mayfield; Julius Bogomolovas; M Roselle Abraham; Kathryn Sullivan; Youngho Seo; Farah Sheikh; Melvin Scheinman

doi:10.1016/j.jacep.2023.04.020

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

JACC Clin Electrophysiol. 2023 Sep;9(9):2024-2033. doi: 10.1016/j.jacep.2023.04.020. Epub 2023 Jul 19.

Authors

Jacob J Mayfield¹, Julius Bogomolovas², M Roselle Abraham³, Kathryn Sullivan⁴, Youngho Seo⁵, Farah Sheikh⁶, Melvin Scheinman⁷

Affiliations

¹ Division of Cardiology, University of Washington, Seattle, Washington, USA; Division of Cardiology, University of California-San Francisco, San Francisco, California, USA.
² Department of Medicine, University of California-San Diego, La Jolla, California, USA.
³ Division of Cardiology, University of California-San Francisco, San Francisco, California, USA; Department of Radiology, University of California-San Francisco, San Francisco, California, USA.
⁴ Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California-San Francisco, San Francisco, California, USA.
⁵ Department of Radiology, University of California-San Francisco, San Francisco, California, USA.
⁶ Department of Medicine, University of California-San Diego, La Jolla, California, USA. Electronic address: fasheikh@health.ucsd.edu.
⁷ Division of Cardiology, University of California-San Francisco, San Francisco, California, USA. Electronic address: Melvin.Scheinman@ucsf.edu.

PMID: 37480874
DOI: 10.1016/j.jacep.2023.04.020

Abstract

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.

Keywords: arrhythmogenic cardiomyopathy; desmosome; myocarditis.

Publication types

Review