Role of ¦Â₁-adrenoceptor autoantibodies in the pathogenesis of dilated cardiomyopathy

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• 作者：Michael Dandel ; ^{dandel@dhzb.de} ; Gerd Wallukat ; Evgenij Potapov ; Roland Hetzer
• 关键词：Autoantibodies ; ¦Â1 receptors ; Dilated cardiomyopathy ; Pathogenesis ; Immunoadsorption
• 刊名：Immunobiology
• 出版年：2012
• 出版时间：May, 2012
• 年：2012
• 卷：217
• 期：5
• 页码：511-520
• 全文大小：688 K

文摘

Dilated cardiomyopathy (DCM) is a common cause of heart failure. After the identification of several immune regulatory abnormalities in DCM increasing attention has been focused on autoimmune mechanisms as potential key elements in the pathogenesis of the disease. DCM has appeared to be often related to elevated levels of autoantibodies against cardiac structural or functional proteins. Among several autoantibodies (AABs) which react against cardiac cellular proteins that have been detected in sera from DCM patients, those against ¦Â1-adrenoreceptors (¦Â1-ARs) appeared particularly relevant from a pathophysiological point of view. The available experimental and clinical data suggest that in ¦Â1-AAB-positive patients with DCM the cardiomyopathy might be a ¦Â1-AR-targeted autoimmune disease.

This review summarizes the present knowledge about ¦Â1-AABs, their role in DCM etiopathogenesis and the therapeutic benefits of ¦Â1-AAB removal. Special attention is focused on the possible origin of ¦Â1-AABs, their interaction with the ¦Â₁-ARs, the prevalence of ¦Â1-AABs in patients with DCM and the potential pathophysiologic impact of these AABs in the development and progression of the disease. Attention is also given to the amelioration of ¦Â1-AAB cardiotoxicity by ¦Â₁-AR antagonists and especially to immunoadsorption (IA) therapy. Responsiveness to IA therapy and its long-term efficiency, as well as post-IA reappearance of ¦Â₁-AABs and its impact on patients?outcome are also discussed in detail. Finally the important question of whether the therapeutic results of IA are indeed related to ¦Â₁-AAB removal is analyzed on the basis of available data.

Overall the review aims to provide an exhaustive overview of the available experimental and clinical data on ¦Â₁-AABs in DCM and also a theoretical and practical basis for clinicians who are or intend in future to be engaged in this field.