Copyright © 2004 by the European Society of Cardiology.
Clinical research
Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy
a Department of Medicine, Kitasato Institute Hospital, Tokyo, Japan
b Department of Medicine, Keio University School of Medicine, Tokyo, Japan
c Center for Clinical Pharmacy and Clinical Sciences, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan
d Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden
* Corresponding author. Present address: Department of Cardiology, Kitasato Institute Hospital, 5-9-1 Shirokane Minato-ku, Tokyo, Japan. Tel.: +81-3-3444-6161; fax: +81-3-3448-0553
E-mail address: baba-a{at}kitasato.or.jp
Received 2 December 2003; revised 22 April 2004; accepted 12 May 2004 See page 1091 for the editorial comment on this article1
Abstract
Aim To characterise the clinical significance of M2-muscarinic acetylcholine receptor autoantibodies (M2-AAB) in patients with dilated cardiomyopathy (DCM).
Methods and results Sera from 104 patients with DCM, age-matched with 104 patients with idiopathic atrial fibrillation (Af) and 104 healthy control subjects, were screened for M2-AAB by enzyme-linked immunosorbent assay (ELISA). IgG purified by Protein-A column was also used as a primary antibody in ELISA. In DCM, M2-AAB were detected in 40% of patients using whole sera and in 36% of patients using purified IgG. M2-AAB were also found in several patients with idiopathic Af (23%, 23%), and these frequencies were significantly higher than those in healthy subjects (8%, 8%). Af was more common in AAB-positive than in AAB-negative patients with DCM. Multivariable analysis confirmed that M2-AAB were independent predictors of the presence of Af in such patients. We determined electrophysiological changes by adding patient purified M2-AAB to chick embryos. Purified IgG from both Af and DCM patients exhibited negative chronotropic effects and induced supraventricular arrhythmias.
Conclusion M2-AAB may play a role in mediating the development of Af in patients with DCM.
Key Words: Dilated cardiomyopathy • Autoantibodies • Atrial fibrillation
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