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lüll Cardiac troponins and autoimmunity: their role in the pathogenesis of myocarditis and of heart failure Kaya Z; Katus HA; Rose NRClin Immunol 2010[Jan]; 134 (1): 80-8Despite the widespread use of cardiac troponins as biomarkers for the diagnosis and quantitation of cardiac injury, the effect of troponin release and a possible autoimmune response to the troponins is unknown. Other investigators reported that programmed cell death-1 (PD-1)-receptor deficient mice developed severe cardiomyopathy with autoantibodies to troponin I. We found that immunization of genetically susceptible mice with troponin I but not troponin T induced a robust autoimmune response leading to marked inflammation and fibrosis in the myocardium. At later times, antibodies to cardiac myosin were detected in troponin-immunized mice. The severity of inflammation correlated with expression of chemokines RANTES, MIP-2, IP-10 and MCP-1 in the myocardium. Prior immunization with troponin I increased the severity of experimental infarctions, indicating that an autoimmune response to troponin I aggravates acute cardiac damage. Cardiac inflammation, fibrosis and functional impairment were transferred from immunized to naive recipients by CD4+ T cells, and the cytokine profile suggested both Th2 and Th17 profiles in A/J mice. Finally we identified an 18-mer of troponin I containing an immuno-dominant epitope.|Animals[MESH]|Autoimmunity/*immunology[MESH]|Cardiomyopathies/immunology/metabolism[MESH]|Disease Models, Animal[MESH]|Heart Failure/*immunology/metabolism[MESH]|Humans[MESH]|Mice[MESH]|Myocarditis/*immunology/metabolism[MESH]|Myocardium/immunology/metabolism/pathology[MESH]|Troponin/*immunology/metabolism[MESH] |