β1-Adrenoreceptor Autoantibodies in Heart Failure Physiology and Therapeutic Implications

被引:36
作者
Duengen, Hans-Dirk [1 ,9 ]
Dordevic, Aleksandar [1 ]
Felix, Stephan B. [2 ]
Pieske, Burkert [1 ,3 ,4 ,5 ,6 ]
Voors, Adriaan A. [7 ]
McMurray, John J., V [8 ]
Butler, Javed [1 ,9 ]
机构
[1] Charite, Campus Virchow Klinikum, Dept Internal Med & Cardiol, Berlin, Germany
[2] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany
[3] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany
[4] DZHK German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany
[5] Berlin Inst Hlth, Berlin, Germany
[6] German Heart Ctr Berlin, Dept Internal Med & Cardiol, Berlin, Germany
[7] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands
[8] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland
[9] Univ Mississippi, Dept Med, Jackson, MS 39216 USA
关键词
adrenergic; autoantibodies; cardiomyopathies; heart failure; peptides; receptors; BETA(1)-ADRENERGIC RECEPTOR AUTOANTIBODIES; SUBSEQUENT IMMUNOGLOBULIN SUBSTITUTION; IN-VITRO SELECTION; DILATED CARDIOMYOPATHY; PATHOGENIC AUTOANTIBODIES; SUCCESSFUL PROOF; IMMUNOADSORPTION; NEUTRALIZATION; ANTIBODIES; APTAMERS;
D O I
10.1161/CIRCHEARTFAILURE.119.006155
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antibodies that activate the beta(1)-AR (beta(1)-adrenoreceptor) can induce heart failure in animal models. These antibodies are often found in patients with heart failure secondary to varying etiologies. Their binding to the beta(1) receptor leads to prolonged receptor activation with subsequent induction of cellular dysfunction, apoptosis, and arrhythmias. beta-blocker therapy while highly effective for heart failure, may not be sufficient treatment for patients who have beta(1) receptor autoantibodies. Removal of these autoantibodies by immunoadsorption has been shown to improve heart failure in small studies. However, immunoadsorption is costly, time consuming, and carries potential risks. An alternative to immunoadsorption is neutralization of autoantibodies through the intravenous application of small soluble molecules, such as peptides or aptamers, which specifically target and neutralize beta(1)-AR autoantibodies. Peptides may induce immunogenicity. Animal as well as early phase human studies with aptamers have not shown safety concerns to date and have demonstrated effectiveness in reducing autoantibody levels. Novel aptamers have the potential advantage of having a wide spectrum of action, neutralizing a variety of known circulating G-protein coupled receptor autoantibodies. These aptamers, therefore, have the potential to be novel therapeutic option for patients with heart failure who have positive for beta(1)-AR autoantibodies. However, clinical outcomes trials are needed to assess the clinical utility of this novel approach to treat heart failure.
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页数:9
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