Autoantibodies to cardiac troponin I in patients with idiopathic dilated and ischemic cardiomyopathy

Background: Progressive dilatation and functional compromise of heart function is attributed to a variety of pathogenic mechanisms. Experimental data suggests that autoantibodies could promote myocardial damage by inducing either inflammation or alternatively, augmentation of Ca²⁺ currents or activation of surface receptors on cardiomyocytes. Cardiac troponin I (cTpnI) is an essential protein component of the contractile heart. Herein, we studied the presence and functional properties of autoantibodies to cTpnI in patients with idiopathic dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). Methods and results: Anti-cTpnI antibody ELISA was established for assessment of sera obtained from 33 patients with ICM, 32 with DCM and 42 healthy subjects. Binding specificity of purified cTpnI-reactive IgG fractions from patients with ICM and DCM was confirmed by competitive inhibition studies employing fluid-phase cTpnI. The effect of IgG preparations on intracellular Ca²⁺ ([Ca²⁺]_i) transients was tested in cultured neonatal rat ventricular myocytes (NRVM). Six of the 33 ICM patients (18.2%) and 5 of the 32 DCM patients (15.6%) had positive anti-cTpnI antibody titer as compared to none in the healthy subjects. Purified IgG from positive patients appeared specific to cTpnI. IgG preparations reactive with cTpnI did not exhibit measurable effects on [Ca²⁺]_i transients in cultured NRVM nor did they bind the respective cells by direct immunofluorescence. Conclusion: IgG antibodies to TpnI are increased in a significant number of patients with both ICM and idiopathic DCM, yet it appears that these autoantibodies cannot bind heart muscle cells or influence [Ca²⁺]_i transients.