Abstract
Dilated cardiomyopathy is a severe pathology of the heart with poorly understood etiology. Disruption of the gene encoding the negative immunoregulatory receptor PD-1 in BALB/c mice, but not in BALB/c RAG-2-/- mice, caused dilated cardiomyopathy with severely impaired contraction and sudden death by congestive heart failure. Affected hearts showed diffuse deposition of immunoglobulin G (IgG) on the surface of cardiomyocytes. All of the affected PD-1-/- mice exhibited high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes. These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Surface / genetics
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Antigens, Surface / physiology*
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Apoptosis Regulatory Proteins
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Autoantibodies / analysis*
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Autoantibodies / blood
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Autoantigens / chemistry
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Autoantigens / immunology
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / pathology
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Autoimmune Diseases / physiopathology
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Cardiomyopathy, Dilated / immunology*
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Cardiomyopathy, Dilated / pathology
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Cardiomyopathy, Dilated / physiopathology
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Complement C3 / analysis
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Echocardiography
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Heart Failure / etiology
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Immunoglobulin G / analysis
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Immunoglobulin G / blood
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Membrane Proteins / chemistry
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Membrane Proteins / immunology
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Mice
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Mice, Inbred BALB C
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Molecular Weight
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Myocardium / immunology*
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Myocardium / pathology
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Programmed Cell Death 1 Receptor
Substances
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Antigens, Surface
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Apoptosis Regulatory Proteins
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Autoantibodies
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Autoantigens
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Complement C3
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Immunoglobulin G
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Membrane Proteins
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Pdcd1 protein, mouse
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Programmed Cell Death 1 Receptor