Anti-RNApol3-Associated myocarditis: an emerging disease linking autoimmunity and infection.

Background: Fulminant myocarditis (FM) is a severe condition primarily triggered by viruses. Anti-RNA polymerase III autoantibodies (RNApol3) which are typically found in patients with severe systemic sclerosis, have been reported in patients with influenza-related FM. Our objective is to provide additional insight into RNApol3-associated FM.

Methods: We retrospectively included all patients admitted to our institution between January 2013 and June 2023 with acute myocarditis and positive serum RNApol3. We compared their characteristics, etiologies, and outcomes with those of a cohort of RNApol3 negative acute myocarditis.

Results: Twenty-nine RNApol3-positive patients, comprising 83% females with a mean age of 39 ± 12 years, were included in this study. Each patient was admitted to the intensive care unit at least once and 11 (38%) relapsed. Triggers included influenza virus in 55% and SARS-CoV-2 virus in 48% of cases. The lowest left ventricular ejection fraction was 10 [5-10] % and the highest troponin value was 82 [22-360] times the ULN. Patients required dobutamine (94%), veno-arterial extracorporeal membrane oxygenation (85%) and pericardiocentesis (38%). At the last follow-up, 76% of patients were still alive, while 7% had undergone cardiac transplantation, and 3% required a left ventricular assist device. Compared to RNApol3-negative cases, RNApol3-positive myocarditis was associated with female gender, fulminant evolution, tamponade, a higher likelihood of being caused by a proven viral infection, and a higher rate of relapse.

Conclusion: RNApol3-associated myocarditis is an emerging disease linking autoimmunity and infection and a unique cause of acquired, pathogen-specific, organ-specific immunodeficiency. RNApol3 should be screened in all cases of FM, especially in young women infected by RNA viruses. The risk of FM in RNApol3-positive systemic sclerosis needs further investigation.