title: Cardiac troponins and autoimmunity: their role in the pathogenesis of myocarditis and of heart failure.
abstract: Despite 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.
authors.affiliation: Department of Cardiology, University of Heidelberg, 69120 Heidelberg, Germany. ziya.kaya@med.uni-heidelberg.de
authors.forename: Ziya
authors.initials: Z
authors.lastname: Kaya
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D009202:Cardiomyopathies / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006333:Heart Failure / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014336:Troponin / Q000276:immunology* / Q000378:metabolism
chemical_list: D014336:Troponin