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...

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Hauptverfasser: Kaya, Ziya (VerfasserIn) , Katus, Hugo (VerfasserIn) , Rose, Noel R. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2010
In: Clinical immunology
Year: 2010, Jahrgang: 134, Heft: 1, Pages: 80-88
ISSN:1521-7035
DOI:10.1016/j.clim.2009.04.008
Online-Zugang:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.clim.2009.04.008
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S152166160900638X
Volltext
Verfasserangaben:Ziya Kaya, Hugo A. Katus, Noel R. Rose

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520 |a 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. 
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