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AUTOANTIBODY PROFILING IN CARDIOVASCULAR DISEASES AND IDENTIFICATION OF NEW TARGETS
A969 JACC April 1, 2014 Volume 63, Issue 12
Heart Failure and Cardiomyopathies Autoantibody Profiling in Cardiovascular Diseases and Identification of New Targets Poster Contributions Hall C Monday, March 31, 2014, 9:45 a.m.-10:30 a.m.
Session Title: Inflammation in Heart Failure Abstract Category: 13. Heart Failure and Cardiomyopathies: Basic Presentation Number: 1262-206 Authors: Anna-Maria Müller, Georgi Hristov, Christel WeiB, Anna Bangert, Renate Öttl, Evangelos Giannitsis, Hugo Katus, Ziya Kaya, University Clinic Heidelberg, Cardiology, Heidelberg, Germany Background: Heart diseases are the leading causes of death worldwide. Dilated cardiomyopathy (DCM), myocarditis and ischemic cardiomyopathy (ICM) can be caused by various factors. After disease onset a dysregulation of the immune system is believed to play a central role in disease progression. Autoantibodies directed against various peptide-antigens present in cardiac tissue are found in these three cardiac diseases. Methods and Results: PEPperMAP Peptide Array analysis with sera obtained from 10 DCM, 10 myocarditis and 10 ICM patients vs. 10 healthy, age-matched controls was performed against 26,364 different 15-mer peptides derived from 166 antigens associated with cardiovascular diseases. All study participants were male. The LV-function of DCM, myocarditis and ICM patients was severely impaired. The top target antigens discovered in the myocarditis group are the giant sarcomeric signaling protein obscurin, the cytoplasmic protein dystrophin and laminin which is present in the basal lamina, as well as regulatory enzymes such as myosin light chain kinase and sodium/potassium transporting ATPase. Regarding DCM, the most promising candidate antigens were the structural proteins obscurin, dystrophin and laminin. In fact, as many as 32% of the top 50 antigenic peptides represent obscurin. In addition, we also identified 4 strongly reacting antigenic oligopeptides derived from RNA-binding protein 20. Sera from ICM patients reacted strongly to peptides derived from laminin, sodium/potassium transporting ATPase located in the plasma membrane and the voltage-gated potassium channel KCNQ1. Among other potential autoantigens in ICM, we could identify the heat shock protein HSP27, the AMP/ ATP-binding subunit of the AMP-activated protein kinase, and actin. Conclusions: In this study, novel target antigens for autoantibody binding in different cardiac diseases have been identified. Some antigens occur in more than one disease. The pathogenity of this autoantibody binding should be tested in animal models. The results of this study can help to establish testing methods for risk stratification in patients and to design more efficient and more specific treatment methods.
Heart Failure and Cardiomyopathies Autoantibody Profiling in Cardiovascular Diseases and Identification of New Targets Poster Contributions Hall C Monday, March 31, 2014, 9:45 a.m.-10:30 a.m.
Session Title: Inflammation in Heart Failure Abstract Category: 13. Heart Failure and Cardiomyopathies: Basic Presentation Number: 1262-206 Authors: Anna-Maria Müller, Georgi Hristov, Christel WeiB, Anna Bangert, Renate Öttl, Evangelos Giannitsis, Hugo Katus, Ziya Kaya, University Clinic Heidelberg, Cardiology, Heidelberg, Germany Background: Heart diseases are the leading causes of death worldwide. Dilated cardiomyopathy (DCM), myocarditis and ischemic cardiomyopathy (ICM) can be caused by various factors. After disease onset a dysregulation of the immune system is believed to play a central role in disease progression. Autoantibodies directed against various peptide-antigens present in cardiac tissue are found in these three cardiac diseases. Methods and Results: PEPperMAP Peptide Array analysis with sera obtained from 10 DCM, 10 myocarditis and 10 ICM patients vs. 10 healthy, age-matched controls was performed against 26,364 different 15-mer peptides derived from 166 antigens associated with cardiovascular diseases. All study participants were male. The LV-function of DCM, myocarditis and ICM patients was severely impaired. The top target antigens discovered in the myocarditis group are the giant sarcomeric signaling protein obscurin, the cytoplasmic protein dystrophin and laminin which is present in the basal lamina, as well as regulatory enzymes such as myosin light chain kinase and sodium/potassium transporting ATPase. Regarding DCM, the most promising candidate antigens were the structural proteins obscurin, dystrophin and laminin. In fact, as many as 32% of the top 50 antigenic peptides represent obscurin. In addition, we also identified 4 strongly reacting antigenic oligopeptides derived from RNA-binding protein 20. Sera from ICM patients reacted strongly to peptides derived from laminin, sodium/potassium transporting ATPase located in the plasma membrane and the voltage-gated potassium channel KCNQ1. Among other potential autoantigens in ICM, we could identify the heat shock protein HSP27, the AMP/ ATP-binding subunit of the AMP-activated protein kinase, and actin. Conclusions: In this study, novel target antigens for autoantibody binding in different cardiac diseases have been identified. Some antigens occur in more than one disease. The pathogenity of this autoantibody binding should be tested in animal models. The results of this study can help to establish testing methods for risk stratification in patients and to design more efficient and more specific treatment methods.