Journal
CLINICAL IMMUNOLOGY
Volume 134, Issue 1, Pages 80-88Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2009.04.008
Keywords
Inflammation; Cardiac troponins; Biomarkers; Fibrosis; Myocardium; Myosin; Cytokine; Cardiomyopathy; Immuno-dominant epitope
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Funding
- Deutsche Forschungsgemeinschaft [KA 1797/3-1, KA 1974/4-1]
- Ernst und Berta Grimmke Stiftung
- National Institutes of Health [HL067290, HL077611]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL067290, R01HL077611, R56HL077611] Funding Source: NIH RePORTER
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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. (C) 2009 Elsevier Inc. All. rights reserved.
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