Cardiac cytotoxic mechanism mediated by antibodies against myocardial mitochondrial ADP/ATP carrier in patients with dilated cardiomyopathy.

OBJECTIVE

To investigate mechanism of the antibody-mediated cardiac cytotoxicity and clinical significance in dilated cardiomyopathy (DCM), and study the effects of the antibodies against the myocardial mitochondrial ADP / ATP carrier from sera of patients with dilated cardiomyopathy on the guinea pig ventricular myocytes.

PATIENTS AND METHODS

This study included 18 patients with DCM (12 men and 6 women), with mean age of 43 years. Control group included 18 health donors, (9 men and 9 women), with mean age of 32 years. The antibodies against the ADP / ATP carrier and cell membrane 52 000 peptide were examined by immunoblotting. The antibody-mediated cardiac cytotoxicity was studied with the cytotoxic test and whole cell patch-clamp technique.

RESULTS

The antibodies against myocardial mitochondrial ADP / ATP carrier and cell membrane 52 000 peptide were positive in 18 patients with DCM, while negative in controls. The antibodies induced cytotoxic damage with time-dependent and enhanced Ca-current in cardiac myocytes. The increasing amplitude of peak Ca(2+)-current was 100 pA-840 pA (n = 8) in different dilution of the antibodies. The effect of the antibodies might be inhibited by verapamil, and were null in controls (n = 4).

CONCLUSIONS

The above findings suggest that an increase in the antibody-mediated Ca(2+)-current of cardiac myocytes is related to the cytotoxic damage in dilated cardiomyopathy.