Cardiac troponins and autoimmunity: Their role in the pathogenesis of myocarditis and of heart failure

Ziya Kaya, Hugo A. Katus, Noel R. Rose

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalClinical Immunology
Volume134
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Biomarkers
  • Cardiac troponins
  • Cardiomyopathy
  • Cytokine
  • Fibrosis
  • Immuno-dominant epitope
  • Inflammation
  • Myocardium
  • Myosin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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