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Cardiac myosin induces myocarditis in genetically predisposed mice
1Department of Immunology and Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
Journal of Immunology (Baltimore, Md. : 1950)
|December 1, 1987
Summary
Cardiac myosin directly causes autoimmune myocarditis in susceptible mice, mirroring coxsackievirus B3 infection. Genetic factors influence susceptibility to this heart disease.
Area of Science:
- Immunology
- Cardiology
- Genetics
Background:
- Coxsackievirus B3 (CVB3) infection can trigger autoimmune myocarditis in mice, linked to myosin autoantibodies.
- The role of cardiac myosin as a direct autoantigen in myocarditis is not fully understood.
Purpose of the Study:
- To investigate whether cardiac myosin itself can induce myocarditis and autoantibody production.
- To identify genetic factors influencing susceptibility to cardiac myosin-induced myocarditis.
Main Methods:
- Immunization of different H-2 congenic mouse strains with purified cardiac myosin.
- Assessment of myocarditis development, myosin autoantibody titers, and autoantibody specificity.
- Analysis of genetic linkage to the major histocompatibility complex (MHC) and other genes.
Main Results:
- Cardiac myosin immunization induced severe myocarditis and high titers of cardiac myosin-specific autoantibodies in susceptible mouse strains (A/J, A.SW/SnJ, A.CA/SnJ).
- Mice resistant to cardiac myosin-induced myocarditis (C57BL/6J, C57BL/10J) did not develop autoantibodies.
- Susceptibility to myocarditis was influenced by MHC-linked and non-MHC-linked genes.
Conclusions:
- Cardiac myosin is a potent autoantigen capable of inducing experimental autoimmune myocarditis (EAM).
- This cardiac myosin-induced myocarditis model closely mimics CVB3-induced myocarditis, offering insights into autoimmune heart disease mechanisms.
- Genetic background plays a critical role in determining susceptibility to autoimmune myocarditis.