Tschöpe Carsten, Van Linthout Sophie, Spillmann Frank, Posch Maximilian G, Reinke Petra, Volk Hans-Dieter, Elsanhoury Ahmed, Kühl Uwe
Department of Cardiology, Charité, University Medicine Berlin, Humboldt-Universität zu Berlin, Campus Virchow, Berlin, Germany.
Experimental Immunocardiology, BCRT - Berlin Institute of Health Center for Regenerative Therapies, Augustenburger Platz 1, Berlin, Germany.
Eur Heart J Case Rep. 2019 Sep 1;3(3). doi: 10.1093/ehjcr/ytz131.
The aetiology of dilated cardiomyopathy (DCM) is highly heterogeneous including genetic and/or acquired (infective, toxic, immune, endocrine, and nutritional) factors. The major part of acquired DCM in developed countries is caused by either viral or autoimmune myocarditis. It is believed that the activation of the T-lymphocyte cell system is the major pathomechanism underlying autoimmune myocarditis and inflammatory DCM (DCMi). However, in the hearts of a subset of patients, a significant number of CD20+ B-lymphocytes can be detected too. Limited information exists on the role of B-cell-dependent mechanisms in the progression of DCMi. Particularly CD20+ B-lymphocytes, which can be targeted by anti-CD20+ B-lymphocytes antibodies or inhibitors, might contribute to the pathogenesis of myocardial damage beyond antibody production.
Here, we present a case series of six patients with subacute and chronic endomyocardial biopsy-proven CD20+ B-lymphocyte-associated DCMi, where symptomatic heart failure therapy, with or without combined immunosuppressive therapy with steroid-based treatment regime, was insufficient to improve cardiac function. Five patients improved clinically several weeks after a standard infusion protocol with rituximab, a chimeric monoclonal antibody against the pan-B-cell surface molecule CD20.
Our case series shows that CD20+ B-lymphocyte persistence can play a pathophysiologic role in a subset of DCMi patients and highlights the potential of targeting CD20+ B cells in patients with prominent CD20+ B-lymphocyte persistence.
扩张型心肌病（DCM）的病因高度异质性，包括遗传和/或后天（感染、中毒、免疫、内分泌和营养）因素。在发达国家，后天性DCM的主要部分由病毒性或自身免疫性心肌炎引起。据信，T淋巴细胞系统的激活是自身免疫性心肌炎和炎症性DCM（DCMi）的主要病理机制。然而，在一部分患者的心脏中，也可检测到大量CD20 + B淋巴细胞。关于B细胞依赖性机制在DCMi进展中的作用，现有信息有限。特别是CD20 + B淋巴细胞，可被抗CD20 + B淋巴细胞抗体或抑制剂靶向，可能在心肌损伤的发病机制中发挥作用，而不仅仅是产生抗体。
在此，我们报告一例系列病例，六例经心内膜活检证实为CD20 + B淋巴细胞相关DCMi的亚急性和慢性患者，其症状性心力衰竭治疗，无论是否联合基于类固醇治疗方案的免疫抑制治疗，均不足以改善心脏功能。五例患者在接受针对泛B细胞表面分子CD20的嵌合单克隆抗体利妥昔单抗的标准输注方案数周后临床症状改善。
我们的病例系列表明，CD20 + B淋巴细胞持续存在可在一部分DCMi患者中发挥病理生理作用，并突出了在CD20 + B淋巴细胞持续存在显著的患者中靶向CD20 + B细胞的潜力。
