Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice

• Published in: Science (American Association for the Advancement of Science) 2001-01, Vol.291 (5502), p.319-322
• Main Authors: Nishimura, Hiroyuki, Okazaki, Taku, Tanaka, Yoshimasa, Nakatani, Kazuki, Hara, Masatake, Matsumori, Akira, Sasayama, Shigetake, Mizoguchi, Akira, Hiai, Hiroshi, Minato, Nagahiro, Honjo, Tasuku
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antigens; Antigens, Surface - genetics; Antigens, Surface - physiology; Apoptosis Regulatory Proteins; Autoantibodies; Autoantibodies - analysis; Autoantibodies - blood; Autoantigens - chemistry; Autoantigens - immunology; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmune Diseases - physiopathology; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiomyopathy, Dilated - immunology; Cardiomyopathy, Dilated - pathology; Cardiomyopathy, Dilated - physiopathology; Cardiovascular disease; Causes of; Complement C3 - analysis; Congestive cardiomyopathy; Dilated cardiomyopathy; Echocardiography; Environmental Influences; Etiology; Genes; Heart; Heart diseases; Heart Failure - etiology; Immunoglobulin G - analysis; Immunoglobulin G - blood; Medical sciences; Membrane Proteins - chemistry; Membrane Proteins - immunology; Mice; Mice, Inbred BALB C; Molecular Weight; Myocarditis. Cardiomyopathies; Myocardium; Myocardium - immunology; Myocardium - pathology; Neurons; Patients; PD-1 gene; PD-1 protein; Programmed Cell Death 1 Receptor; RAG-2 gene; Rodents
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.291.5502.319

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/cRAG-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-kilo-dalton 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.