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

Haim Shmilovich, Asaf Danon, Ofer Binah, Arie Roth, Gerald Chen, Dov Wexler, Gad Keren, Jacob George*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)198-203
Number of pages6
JournalInternational Journal of Cardiology
Volume117
Issue number2
DOIs
StatePublished - 25 Apr 2007

Keywords

  • Autoantibodies
  • Calcium currents
  • Dilated cardiomyopathy
  • Ischemia
  • Troponin I

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