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

Area of Science:

• Cardiology
• Genetics
• Immunology

Background:

• Myocarditis often follows viral infections.
• An association exists between myocarditis and inherited cardiomyopathies, but its nature is unclear.
• Desmosomal variants are implicated in cardiomyopathies.

Purpose of the Study:

• To investigate the link between recurrent myocarditis and pathogenic desmosomal variants.
• To explore potential mechanisms driving myocarditis in genetically predisposed individuals.

Main Methods:

• Presentation of a primary clinical vignette.
• Analysis of a case series of patients with recurrent myocarditis and desmosomal variants.
• Review of clinical and basic science literature.

Main Results:

• Patients with recurrent myocarditis were identified with pathogenic desmosomal variants.
• Two hypotheses were explored: 1) stress-induced myocyte injury in abnormal hearts, and 2) 'two-hit' model involving viral triggers and desmosomal protein dysfunction leading to autoimmunity.

Conclusions:

• Recurrent myocarditis may be a clinical manifestation of underlying inherited cardiomyopathies.
• Pathogenic desmosomal variants could predispose individuals to myocarditis through cellular stress or autoimmune mechanisms.
• Further research is needed to elucidate the precise interplay between genetic factors, viral triggers, and autoimmune responses in myocarditis.