Author: ["Taku Okazaki","Yoshimasa Tanaka","Ryosuke Nishio","Tamotsu Mitsuiye","Akira Mizoguchi","Jian Wang","Masayoshi Ishida","Hiroshi Hiai","Akira Matsumori","Nagahiro Minato","Tasuku Honjo"]
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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.Cite this article
Okazaki, T., Tanaka, Y., Nishio, R. et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med 9, 1477–1483 (2003). https://doi.org/10.1038/nm955 