Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes.
BACKGROUND
Immunoadsorption has been shown to improve cardiac performance and reduce mortality in patients with dilated cardiomyopathy. In this study, the underlying mechanism for these beneficial effects was investigated in cultured rat cardiomyocytes.


RESULTS
Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the beta(1)-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the beta(1)-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the beta(1)-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the beta(1)-selective antagonist bisoprolol and the peptide corresponding to the beta(1)-adrenoceptor. Column eluent from one patient induced apoptosis in nick end labelling test (8.1+/-1.7% vs. 2.9+/-1.2% in control, p<0.05).


CONCLUSIONS
Autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy have a pathophysiological role, as shown by the complement-dependent cytotoxicity and chronotropic action on rat cardiomyocytes. This implies that removal of circulating autoantibodies might be part of the underlying mechanism for improved cardiac function.
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.
Jie
J
Chen
Lisa
L
Larsson
Espen
E
Haugen
Olga
O
Fedorkova
Eva
E
Angwald
Finn
F
Waagstein
Michael
M
Fu
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000920:Antibody-Dependent Cell Cytotoxicity; D001323:Autoantibodies / Q000302:isolation & purification / Q000502:physiology*; D017298:Bisoprolol / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007163:Immunosorbent Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000276:immunology*; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1; D017298:Bisoprolol