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Lethal immunoglobulins: Autoantibodies and sudden cardiac death
Varvara A Ryabkova1, Yuri V Shubik2, Mikhail V Erman2
1Laboratory of the Mosaics of Autoimmunity, Saint Petersburg State University, Saint-Petersburg, Russian Federation.
Insights
Autoantibodies against cardiac proteins may explain some sudden cardiac deaths (SCD) in young individuals, even after genetic testing. These antibodies, particularly against adrenergic and acetylcholine receptors, impact heart function and predict SCD risk.
Area of Science:
- Cardiology
- Immunology
- Pathophysiology
Background:
- Sudden cardiac death (SCD) is a significant cause of mortality, often linked to underlying cardiac conditions.
- A subset of SCD cases, especially in young individuals (<35 years), remains unexplained by conventional post-mortem examinations, including genetic testing.
- Autoantibodies targeting cardiac proteins are increasingly recognized as potential contributors to various heart diseases and unexplained SCD.
Purpose of the Study:
- To review the prevalence and pathophysiological relevance of autoantibodies in cardiac diseases and unexplained SCD.
- To propose a classification for autoantibodies associated with heart conditions.
- To analyze the molecular and cellular effects of these autoantibodies.
Main Methods:
- Analysis of clinical and animal studies investigating autoantibodies in cardiac patients.
- Review of data on autoantibody prevalence and association with different cardiac diseases.
- Examination of molecular and cellular mechanisms of autoantibody action.
Main Results:
- Autoantibodies against beta-adrenergic and muscarinic acetylcholine receptors are independent predictors of SCD in various heart conditions.
- An autoimmune mechanism is suggested for cardiac adverse events post-human papillomavirus (HPV) vaccination, supported by molecular similarities.
- Autoantibodies targeting calcium and potassium ion channels may mimic genetic cardiac channelopathies, contributing to SCD.
Conclusions:
- Autoantibodies represent a crucial, yet often overlooked, factor in the pathogenesis of diverse cardiac diseases and unexplained SCD.
- Targeting specific autoantibodies or the underlying autoimmune processes may offer novel therapeutic strategies for preventing SCD.
- Further research into autoimmune mechanisms is warranted for unexplained SCD and vaccine-related cardiac events.
Abstract:
Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. Patients with cardiomyopathies, myocarditis, ischemic heart disease and cardiac channelopathies are at risk of SCD. However, a certain percentage of autopsy-negative cases of SCD in the young (<35 years) remain unexplained even after a post-mortem genetic testing. Autoantibodies against cardiac proteins may be potentially involved in the pathogenesis of different heart diseases and in the occurrence of unexplained SCD. In this review we analyze clinical and animal studies that elucidate the prevalence of these autoantibodies in patients with different cardiac diseases and their pathophysiological relevance. We propose a classification of the autoantibodies associated with heart diseases and focus on their molecular and cellular effects. Anti-beta adrenergic receptor antibodies and anti-muscarinic acetylcholine receptor antibodies affect myocardial electrophysiological properties and were reported to be the independent predictors of SCD in patients with different heart diseases. Autoimmune mechanism is proposed for cardiac-related adverse reactions following human papillomavirus (HPV) vaccination. The pentapeptid sharing between HPV's antigens, adrenergic receptors and muscarinic acetylcholine receptors supports this assumption. The dysregulating effects of the autoantibodies against calcium and potassium ion channels can be the basis for autoimmune phenocopies of genetic cardiac channelopathies, which are also associated with SCD.
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