Doberman pinschers present autoimmunity associated with functional autoantibodies: A model to study the autoimmune background of human dilated cardiomyopathy

Wess, Gerhard; Wallukat, Gerd; Fritscher, Anna; Becker, Niels-Peter; Wenzel, Katrin; Müller, Johannes und Schimke, Ingolf (2019): Doberman pinschers present autoimmunity associated with functional autoantibodies: A model to study the autoimmune background of human dilated cardiomyopathy.
In: PLOS One 14(7), e0214263

Abstract

Background Autoimmunity associated with autoantibodies against the beta 1-adrenergic receptor (beta 1-AAB) is increasingly accepted as the driver of human dilated cardiomyopathy (DCM). Unfortunately, there is a lack of animal models to extend the knowledge about beta 1-AAB autoimmunity in DCM and to develop appropriate treatment strategies. Objectives To introduce an animal model, we investigated the beta 1-AAB associated autoimmunity in Doberman Pinscher (DP) with dilated cardiomyopathy, which has similarities to human DCM. Materials and methods Eighty-seven DP with cardiomyopathy in terms of pathological ECG and echocardiography (DoCM) and 31 dogs (at enrollment) without DoCM (controls) were analyzed for serum activity of beta 1-AAB with a bioassay that records the chronotropic response of spontaneously beating cultured neonatal rat cardiomyocytes to the DP's IgG. To locate the receptor binding site of beta 1-AAB and the autoantibody's sensitivity to inhibition, competing experiments with related blockers were performed with the bioassay. In controls that developed DoCM during follow-up, beta 1-AAB were analyzed during progress. Results Fifty-nine (67.8%) DoCM dogs and 19 (61.3%) controls were beta 1-AAB positive. Of the controls that developed DoCM, 8 were beta 1-AAB positive (p = 0.044 vs. dogs remaining in the control group);their beta 1-AAB activity increased with the cardiomyopathy progress (p< 0.02). To supplement DoCM group with the 9 animals which developed cardiomyopathy in the follow up, a more pronounced beta 1-AAB positivity became visible in the DoCM group (p = 0.066). Total and cardiac mortality were higher in beta 1-AAB positive DP (p = 0.002;p = 0037). The dogs' beta 1-AAB recognized a specific epitope on the second extracellular receptor and were sensitive to inhibition by drugs already successfully tested to inhibit the corresponding human autoantibody. Conclusions Doberman Pinschers presented beta 1-AAB associated autoimmunity, similar as in the pathogenesis of human DCM. Consequently, DP could compensate the lack of animal models for the investigation of beta 1-AAB autoimmunity in human DCM.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Sprache: Englisch