Antibody-mediated autoimmune myocarditis depends on genetically determined target organ sensitivity.
Injury to cardiac myocytes often leads to the production of anti-myosin antibodies. While these antibodies are a marker of myocardial injury, their contribution to pathogenesis in diseases such as autoimmune myocarditis or rheumatic fever is much less clear. We demonstrate in this report that monoclonal anti-myosin antibodies can mediate myocarditis in a susceptible mouse strain. Additionally, we show disease susceptibility depends on the presence of myosin or a myosin-like molecule in cardiac extracellular matrix. This study demonstrates that susceptibility to autoimmune heart disease depends not only on the activation of self-reactive lymphocytes but also on genetically determined target organ sensitivity to autoantibodies.
Liao
L
L
Albert Einstein College of Medicine, Bronx, New York 10461.
Sindhwani
R
R
Rojkind
M
M
Factor
S
S
Leinwand
L
L
Diamond
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016326:Extracellular Matrix Proteins / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000235:genetics* / Q000276:immunology; D009218:Myosins / Q000276:immunology*; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D009218:Myosins