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

Abstract	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.
Authors	Taku Okazaki, Yoshimasa Tanaka, Ryosuke Nishio, Tamotsu Mitsuiye, Akira Mizoguchi, Jian Wang, Masayoshi Ishida, Hiroshi Hiai, Akira Matsumori, Nagahiro Minato, Tasuku Honjo
Journal	Nature medicine (Nat Med) Vol. 9 Issue 12 Pg. 1477-83 (Dec 2003) ISSN: 1078-8956 [Print] United States
PMID	14595408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Monoclonal Antigens, CD Antigens, Surface Apoptosis Regulatory Proteins Autoantibodies DNA, Complementary PDCD1 protein, human Pdcd1 protein, mouse Programmed Cell Death 1 Receptor Troponin I
Topics	Animals Antibodies, Monoclonal (administration & dosage) Antigens, CD Antigens, Surface (genetics, immunology) Apoptosis Regulatory Proteins Autoantibodies (metabolism) Base Sequence Calcium Signaling Cardiomyopathy, Dilated (etiology, genetics, immunology, metabolism) DNA, Complementary (genetics) Humans Mice Mice, Inbred A Mice, Inbred BALB C Mice, Knockout Mice, Nude Myocytes, Cardiac (immunology, metabolism) Programmed Cell Death 1 Receptor Rats Rats, Wistar Troponin I (immunology)

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