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

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 Ca (2+) current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.