Müller Anna-Maria, Bockstahler Mariella, Hristov Georgi, Weiß Christel, Fischer Andrea, Korkmaz-Icöz Sevil, Giannitsis Evangelos, Poller Wolfgang, Schultheiss Heinz-Peter, Katus Hugo A, Kaya Ziya
Department of Cardiology, University of Heidelberg, 69120 Heidelberg, Germany.
Department of Clinical Statistics, Biomathematics, Information Processing, University of Heidelberg/Mannheim, 68167 Mannheim, Germany.
Clin Immunol. 2016 Dec;173:64-75. doi: 10.1016/j.clim.2016.09.003. Epub 2016 Sep 12.
In myocarditis and dilated cardiomyopathy (DCM) patients the immune system may play an important role in disease progression. In this study, we aimed to identify new antigens as a target for autoimmune response that might play a crucial role in these diseases. Therefore, a peptide-array was used to investigate antibody binding profiles in patients with autoimmune myocarditis or DCM compared to healthy controls and thus to identify disease relevant antigens. To analyze the pathogenicity of the identified antigens, an experimental autoimmune myocarditis (EAM) model was used. Hereby, 3 peptide sequences, derived from myosin-binding-protein-C (MYBPC) fast-type, RNA-binding-protein 20 (RBM20), and dystrophin, showed pathogenic effects on the myocardium of mice. In summary, 3 potentially cardiopathogenic peptides (MYBPC fast-type, RBM20, dystrophin) were identified. Thus, this study could serve as a basis for future investigations aimed at determining further antigens leading to pathogenic effects on the myocardium of DCM as well as myocarditis patients.
在心肌炎和扩张型心肌病（DCM）患者中，免疫系统可能在疾病进展中发挥重要作用。在本研究中，我们旨在鉴定新的抗原，作为自身免疫反应的靶点，这些抗原可能在这些疾病中起关键作用。因此，使用肽阵列研究自身免疫性心肌炎或DCM患者与健康对照相比的抗体结合谱，从而鉴定与疾病相关的抗原。为了分析所鉴定抗原的致病性，使用了实验性自身免疫性心肌炎（EAM）模型。由此，源自肌球蛋白结合蛋白C（MYBPC）快肌型、RNA结合蛋白20（RBM20）和肌营养不良蛋白的3个肽序列对小鼠心肌显示出致病作用。总之，鉴定出了3种潜在的致心肌病变肽（MYBPC快肌型、RBM20、肌营养不良蛋白）。因此，本研究可为未来旨在确定对DCM以及心肌炎患者心肌产生致病作用的其他抗原的研究提供基础。
