Cardiac troponins and autoimmunity: their role in the pathogenesis of myocarditis and of heart failure.
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.
Kaya
Ziya
Z
Department of Cardiology, University of Heidelberg, 69120 Heidelberg, Germany. ziya.kaya@med.uni-heidelberg.de
Katus
Hugo A
HA
Rose
Noel R
NR
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
D014336:Troponin