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Article
Nature Medicine  9, 1477 - 1483 (2003)
Published online: 2 November 2003; | doi:10.1038/nm955

Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice

Taku Okazaki1, Yoshimasa Tanaka2, 3, Ryosuke Nishio4, 5, Tamotsu Mitsuiye6, Akira Mizoguchi7, Jian Wang1, Masayoshi Ishida2, Hiroshi Hiai8, Akira Matsumori4, Nagahiro Minato2 & Tasuku Honjo1

1  Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.

2  Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.

3  Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama, 332-0012, Japan.

4  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.

5  Division of Emergency Medicine, Kyoto University Hospital, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

6  Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.

7  Department of Anatomy, Graduate School of Medicine, Mie University, Edobashi, Tsu, Mie, 514-8507, Japan.

8  Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.

Correspondence should be addressed to Tasuku Honjo honjo@mfour.med.kyoto-u.ac.jp
We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein. In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.

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REFERENCE
Cardiovascular Disease and Congenital Heart Defects
Nature Encyclopaedia of Life Sciences
 See all 2 matches for Reference

NEWS AND VIEWS
Etiologies of cardiomyopathy and heart failure
Nature Medicine News and Views (01 Mar 1999)

RESEARCH
Heart-specific activation of LTK results in cardiac hypertrophy, cardiomyocyte degeneration and gene reprogramming in transgenic mice
Oncogene Original Article (01 Jul 1999)
Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart
The EMBO Journal Article (25 Feb 2004)
Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m2) cyclophosphamide
Bone Marrow Transplantation Original Article (08 Aug 2001)
 See all 6 matches for Research

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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