Autoimmune Myocarditis, Old Dogs and New Tricks

Circulation Research, Journal Year: 2024, Volume and Issue: 134(12), P. 1767 - 1790

Published: June 6, 2024

Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even cases myocarditis caused viral infections, dysregulated immune responses contribute pathogenesis. However, whether triggered existing conditions or precise antigens immunologic pathways driving remain incompletely understood. The emergence associated with checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity understand mechanisms autoreactive T cells specific cardiac myosin playing a pivotal role. Despite their self-antigen recognition, myosin-specific can be present healthy individuals due bypassing thymic selection stage. In recent studies, novel modalities suppressing activity pathogenic including have proven effective myocarditis. This review offers overview current understanding heart antigens, autoantibodies, underlying various forms along latest updates on clinical management prospects future research.

Language: Английский

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Molecular fingerprints of cardiovascular toxicities of immune checkpoint inhibitors

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 17, 2024

Abstract Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by unleashing the power of immune system against malignant cells. However, their use is associated with a spectrum adverse effects, including cardiovascular complications, which can pose significant clinical challenges. Several mechanisms contribute to toxicity ICIs. First, dysregulation checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1) its ligand (PD-L1), molecular mimicry cardiac autoantigens, leads immune-related events, myocarditis vasculitis. These events result from aberrant activation T cells self-antigens within myocardium or vascular endothelium. Second, disruption homeostasis ICIs lead autoimmune-mediated inflammation tissues, manifesting dysfunction heart failure, arrhythmias, pericarditis. Furthermore, upregulation inflammatory cytokines, particularly tumor necrosis factor-alpha, interferon-γ, interleukin-1β, interleukin-6, interleukin-17 contributes endothelial dysfunction, plaque destabilization, thrombosis, exacerbating risk on long term. Understanding intricate side effects induced crucial for optimizing patient care ensure safe effective integration immunotherapy into broader range treatment protocols. The implications these underscore importance vigilant monitoring early detection in patients receiving Future key pathological mediators biomarkers may aid prompt diagnosis cardiotoxicity will allow timely interventions.

Language: Английский

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Immune checkpoint inhibitor-associated myocarditis: a review of current state of knowledge

The Journal of Cardiovascular Aging, Journal Year: 2025, Volume and Issue: 5(1)

Published: Feb. 28, 2025

Background: Immune checkpoint inhibitors (ICIs) have changed the landscape in oncology, providing effective cancer management for a growing population. However, by promoting an immunological attack on cells, healthy cells may be harmed process. Increased awareness of ICI-associated myocarditis (ICIMy) as one most fatal immune-related adverse events has led to efforts improve diagnosis and treatment this condition. The purpose review is summarize current state knowledge regarding ICIMy. Methods: We performed literature search Pubmed Scopus with relevant keywords, screened titles abstracts results, reviewed selected publications using pre-established criteria. Main findings: Although ICIMy’s cumulative incidence below 0.5% clinical trials, real-world data reveal higher up 4%. Underlying pathophysiologic mechanisms include T cell clonal expansion, molecular mimicry, increased inflammatory cytokine signaling pathways leading presentation can vary from asymptomatic fulminant cardiac death often accompanied musculoskeletal events. Emerging diagnostic tools prognostic value global longitudinal strain assessment multiple PET-CT modalities. mainstay includes holding immunotherapy, prompt high-dose methylprednisolone, close cardiovascular observation. Fulminant refractory cases benefit additional immunomodulatory therapies. Principal conclusions: ICIMy rare event, its non-specific warrants high level suspicion. Once considered likely diagnosis, therapies should initiated promptly.

Language: Английский

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Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis

Nature Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

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Insight of immune checkpoint inhibitor related myocarditis

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113559 - 113559

Published: Nov. 12, 2024

Language: Английский

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