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.


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.
Liao
Y
Y
Institute of Cardiovascular Diseases, Tongji Medical University, Wuhan.
Tu
Y
Y
Chen
L
L
Dai
S
S
Peng
Y
Y
Li
S
S
Zhang
J
J
D000328:Adult; D001323:Autoantibodies / Q000502:physiology*; D015220:Calcium Channels; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000276:immunology*; D009206:Myocardium / Q000166:cytology
D001323:Autoantibodies; D015220:Calcium Channels; D000226:Mitochondrial ADP, ATP Translocases