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

Abstract

BackgroundAutoimmunity associated with autoantibodies directed against the {beta}1-adrenergic receptor ({beta}1-AAB) is increasingly accepted as driving human dilated cardiomyopathy (DCM). Unfortunately, animal models of DCM are lacking, preventing our knowledge about {beta}1-AAB autoimmunity in DCM from being extended and hindering the development of related treatment strategies.\n\nObjectivesTo introduce an animal model, we studied Doberman pinschers, which develop cardiomyopathy (DoCM), with similarities to human DCM, with regard to their {beta}1-AAB autoimmunity.\n\nMethodsEighty-seven DP with DoCM and 31 (at enrolment) healthy controls were analyzed for {beta}1-AAB; the receptor binding site and sensitivity to inhibition were determined. In controls who developed cardiomyopathy during the follow-up, {beta}1-AAB were analyzed during the DoCM progress.\n\nResultsFifty-nine (67.8%) DoCM dogs and 19 (61.3%) controls were {beta}1-AAB positive. Excluding the 9 controls who developed DoCM in the follow-up, {beta}1-AAB positivity tended to be more pronounced in DoCM.\n\nFrom the controls who developed DoCM, 8 were {beta}1-AAB positive (p=0.044 vs. dogs remaining healthy); their {beta}1-AAB level increased with the cardiomyopathy progress. Overall mortality and mortality exclusively due to cardiac reasons during the study period, were higher (p=0.002; p=0037) in {beta}1-AAB positive dogs. The dogs {beta}1-AAB targeted a specific epitope centralized on the second extracellular receptor and were sensitive to inhibition by drugs already successful tested for the corresponding human autoantibody.\n\nConclusionsDoberman pinschers presented {beta}1-AAB associated autoimmunity similar to that driving the pathogenesis of human DCM. Consequently, DP could remove the lack of animal models available for studying {beta}1-AAB autoimmunity in DCM.