© 2006 European Society of Cardiology
Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes
a Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital Göteborg, Sweden
b Department of Cardiology, Xinhua Hospital, Shanghai Second Medical University Shanghai, PR China
c Department of Cardiology, Sahlgrenska University Hospital Göteborg, Sweden
d Department of Medicine, Sahlgrenska University Hospital Göteborg, Sweden
* Corresponding author. Heart Failure Center, Department of Medicine c/o Wallenberg Laboratory, Sahlgrenska University Hospital, SE 41345 Göteborg, Sweden. Tel.: +46 31 3422923; fax: +46 31 823762.Email address: Michael.fu{at}wlab.gu.se
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Abstract |
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Introduction: 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.
Methods and results: Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the β1-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the β1-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the β1-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the β1-selective antagonist bisoprolol and the peptide corresponding to the β1-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).
Conclusion: 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.
Key Words: Autoantibodies • β1-Adrenoceptor • Cytotoxicity • Dilated cardiomyopathy • Immunoadsorption
Received May 18, 2005; Revised July 30, 2005; Accepted October 31, 2005
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