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Detection of DCM-associated β1-adrenergic receptor autoantibodies requires functional readouts or native human β1-receptors as targets

  • Author Footnotes
    1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    Beatrice Bornholz
    Footnotes
    1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    Affiliations
    Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Duesseldorf, Germany
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  • Author Footnotes
    1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    Birgit Hanzen
    Footnotes
    1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    Affiliations
    Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Duesseldorf, Germany
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  • Author Footnotes
    2 These authors contributed to the design of the study, the recruitment of study subjects, analysis of the data and their discussed interpretation.
    Yvonne Reinke
    Footnotes
    2 These authors contributed to the design of the study, the recruitment of study subjects, analysis of the data and their discussed interpretation.
    Affiliations
    Department of Internal Medicine B, University Medicine, Greifswald, Germany

    DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany
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  • Author Footnotes
    2 These authors contributed to the design of the study, the recruitment of study subjects, analysis of the data and their discussed interpretation.
    Stephan B. Felix
    Footnotes
    2 These authors contributed to the design of the study, the recruitment of study subjects, analysis of the data and their discussed interpretation.
    Affiliations
    Department of Internal Medicine B, University Medicine, Greifswald, Germany

    DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany
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  • Author Footnotes
    3 This author contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    Roland Jahns
    Footnotes
    3 This author contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    Affiliations
    Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Germany

    Interdisciplinary Bank of Biomaterials and Data Wurzburg (ibdw), University Hospital of Würzburg, Germany
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  • Author Footnotes
    4 These authors contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    Ingolf Schimke
    Footnotes
    4 These authors contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    Affiliations
    Berlin Cures GmbH, Berlin, Germany
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  • Author Footnotes
    4 These authors contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    Gerd Wallukat
    Footnotes
    4 These authors contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    Affiliations
    Berlin Cures GmbH, Berlin, Germany
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  • Author Footnotes
    5 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    Fritz Boege
    Correspondence
    Corresponding author at: Institute of Clinical Chemistry and Laboratory Diagnostics, University Hospital, Moorenstraße 5, 40225 Düsseldorf, Germany.
    Footnotes
    5 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    Affiliations
    Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Med. Faculty, Duesseldorf, Germany
    Search for articles by this author
  • Author Footnotes
    1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
    2 These authors contributed to the design of the study, the recruitment of study subjects, analysis of the data and their discussed interpretation.
    3 This author contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    4 These authors contributed to the design of the study, the acquisition and analysis of the data and their discussed interpretation.
    5 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Published:October 05, 2015DOI:https://doi.org/10.1016/j.ijcard.2015.10.068
      Today, it has been generally accepted that autoantibodies stimulating the β1-adrenergic receptor (β1AR) play a paramount role in the pathogenesis of several autoimmune-disorders entailing chronic heart failure [
      • Jahns R.
      • Boivin V.
      • Siegmund C.
      • Inselmann G.
      • Lohse M.J.
      • Boege F.
      Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure.
      ,
      • Wallukat G.
      • Schimke I.
      Agonistic autoantibodies directed against G-protein-coupled receptors and their relationship to cardiovascular diseases.
      ]. Potentially cardio-noxious β1AR-autoantibodies can be selectively removed [
      • Dandel M.
      • Wallukat G.
      • Englert A.
      • Hetzer R.
      Immunoadsorption therapy for dilated cardiomyopathy and pulmonary arterial hypertension.
      ] or neutralized in situ [
      • Boivin V.
      • Beyersdorf N.
      • Palm D.
      • Nikolaev V.O.
      • Schlipp A.
      • Muller J.
      • et al.
      Novel receptor-derived cyclopeptides to treat heart failure caused by anti-beta1-adrenoceptor antibodies in a human-analogous rat model.
      ,
      • Haberland A.
      • Wallukat G.
      • Berg S.
      • Schulz A.M.
      • Freyse E.J.
      • Vetter R.
      • et al.
      Neutralization of pathogenic beta1-receptor autoantibodies by aptamers in vivo: the first successful proof of principle in spontaneously hypertensive rats.
      ], but only autoantibody-positive patients will benefit from such interventions [
      • Dandel M.
      • Wallukat G.
      • Englert A.
      • Hetzer R.
      Immunoadsorption therapy for dilated cardiomyopathy and pulmonary arterial hypertension.
      ]. Therefore, the urgently needed key for a broad clinical implementation of therapies specifically directed at β1AR-autoantibodies is a companion diagnostic that enables the selection of autoantibody-positive patients, and the monitoring of autoantibody levels during therapy (response assessment) and follow-up (indication for re-treatment) [
      • Bornholz B.
      • Roggenbuck D.
      • Jahns R.
      • Boege F.
      Diagnostic and therapeutic aspects of beta-adrenergic receptor autoantibodies in human heart disease.
      ].

      Keywords

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