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Antibodies to cardiac receptors

Antikörper gegen kardiale Rezeptoren

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Abstract

Inflammation of cardiac tissue is generally associated with an activation of the host’s immune system. On the one hand, this activation is mandatory to protect the heart by fighting the invading microbial agents or toxins and by engaging myocardial reparation and healing processes. On the other hand, uncontrolled activation of the immune defense has the risk of an arousal of auto- or cross-reactive immune cells, which in some cases bring more harm than good. Dependent on the individual genetic predisposition, such heart-directed autoimmune reactions most likely occur as a result of myocyte apoptosis or necrosis and subsequent liberation of self-antigens previously hidden to the immune system. During the past two decades, evidence for a pathogenic relevance of autoimmunity in human heart disease has substantially increased. Conformational cardiac (auto)antibodies affecting cardiac function and, in particular, (auto)antibodies that target G protein-coupled cardiac membrane receptors are thought to play a key role in the development of heart failure. Clinical pilot studies even suggest that such antibodies negatively affect survival in heart failure patients. However, the true prevalence and clinical impact of many cardiac (auto)antibodies in human heart diseases are still unclear, as are the events triggering their formation, their titer course, and their patterns of clearance and/or persistence. The present article summarizes current knowledge in the field of cardiac receptor (auto)antibodies including recent efforts to address some of the aforementioned gaps of knowledge, thereby attempting to pave the way for novel, more specific therapeutic approaches.

Zusammenfasung

Entzündungsreaktionen im Herzmuskelgewebe sind regelhaft mit einer Aktivierung des Immunsystems verbunden. Diese ist einerseits notwendig, um das Herz selbst vor mikrobiellen Erregern und/oder Toxinen zu schützen und zugleich auch myokardiale Reparatur- und Heilungsprozesse einzuleiten. Andererseits birgt eine überschießende Aktivierung des Immunsystems grundsätzlich das Risiko einer Entstehung von selbst- oder kreuzreaktiven Immunzellen, die unter bestimmten Umständen mehr Schaden als Nutzen anrichten können. Abhängig von der individuellen genetischen Prädisposition entstehen gegen das eigene Herz gerichtete Immunreaktionen vermutlich infolge einer Apoptose oder Nekrose von Myozyten, bei der es zur Freisetzung von dem Immunsystem zuvor nicht bekannten oder zugängigen sog. „Selbstantigenen“ kommt. In den letzten 20 Jahren hat die Evidenz für eine pathogenetische Relevanz solcher, gegen das eigene Herz gerichteten Immunreaktionen bei bestimmten Herzerkrankungen stark zugenommen. Konformationellen (d. h. konformationserkennenden) Autoantikörpern – vor allem solchen, die die Herzfunktion durch Bindung an kardiale G-Protein-gekoppelte Rezeptoren beeinflussen – könnte demnach eine Schlüsselrolle bei der Entstehung der Herzinsuffizienz zukommen. Klinische Pilotstudien deuten sogar darauf hin, dass funktionell aktivierende Rezeptorantikörper die Prognose herzinsuffizienter Patienten deutlich verschlechtern. Dennoch sind die tatsächliche Prävalenz und klinische Relevanz vieler Rezeptorautoantikörper noch immer unklar, ebenso die kardialen Ereignisse, welche die Ausbildung von Rezeptorantikörpern triggern, der Titerverlauf und die Bedingungen, unter denen solche Antikörper persistieren oder spontan verschwinden. Der folgende Beitrag gibt eine kurze Übersicht über den Stand der Wissenschaft auf dem Gebiet der kardialen Rezeptorantikörper und die gegenwärtigen Bemühungen, einen Teil der noch offenen Fragen wissenschaftlich systematisch anzugehen, um damit letztlich den Weg für neue antikörperspezifische Therapieansätze zu ebnen.

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Acknowledgments

The authors of this article receive public funding from the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung, ETiCS-study, BMBF project number 01ES0816). The ETiCS study has been acknowledged by the German Competence Network Heart Failure (CNHF, Subproject 6b), and has equally been associated to the BMBF-funded Comprehensive Heart Failure Centre, University Hospital of Würzburg (CHFC, Subproject C4). All authors had full access to the data and have read and approved the final article.

Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Comprehensive Heart Failure Center (CHFC), University Hospital Würzburg, and Rudolf Virchow Center (RVZ), DFG-Forschungszentrum für Biomedizin, University of Würzburg, Straubmühlweg 2a, 97078, Würzburg, Germany

    V. Boivin-Jahns, A. Schlipp, S. Hartmann, P. Panjwani, M.J. Lohse &  R. Jahns

  2. Comprehensive Heart Failure Centre (CHFC) and Interdisciplinary Bank of Biomaterials and Data Würzburg (ibdw), Würzburg, Germany

    V. Boivin-Jahns, S. Hartmann, M.J. Lohse, G. Ertl &  R. Jahns

  3. Institute of Pathology, Department of Molecular Pathology, University Hospital Tübingen, Tübingen, Germany

    K. Klingel

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  1. V. Boivin-Jahns
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Boivin-Jahns, V., Schlipp, A., Hartmann, S. et al. Antibodies to cardiac receptors. Herz 37, 843–848 (2012). https://doi.org/10.1007/s00059-012-3699-5

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