The Role of the Immune System in Pathobiology and Therapy of Myocarditis: A Review
Cristina Vicenzetto,
Andrea Silvio Giordani,
Caterina Menghi,
Anna Baritussio,
Maria Grazia Peloso Cattini,
Elena Pontara,
Elisa Bison,
Stefania Rizzo,
Monica De Gaspari,
Cristina Basso,
Gaetano Thiene,
Sabino Iliceto,
Renzo Marcolongo,
Alida Linda Patrizia Caforio
Affiliations
Cristina Vicenzetto
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Andrea Silvio Giordani
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Caterina Menghi
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Anna Baritussio
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Maria Grazia Peloso Cattini
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Elena Pontara
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Elisa Bison
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Stefania Rizzo
Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Monica De Gaspari
Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Cristina Basso
Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Gaetano Thiene
Cardiovascular Pathology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Sabino Iliceto
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Renzo Marcolongo
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
Alida Linda Patrizia Caforio
Cardiology and Cardioimmunology Laboratory, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.
