Inflammatory dilated cardiomyopathy (DCMI)
Inflammatory dilated cardiomyopathy (DCMI)
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DOI：
10.1007/s00059-005-2730-5
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发表时间：
2005-09-01
期刊：
影响因子：
1.7
通讯作者：
Pankuweit, S
中科院分区：
文献类型：
--
作者：
Maisch, B;Richter, A;Pankuweit, S
心肌病是一种心肌疾病，由其中心血流动力学和宏观病理学来定义，分为五种主要形式：扩张型（DCM）、肥厚型（HCM）、限制性（RCM）、右室型（RVCM）和不可分类型心肌病（NCCM）。此外，最新的WHO/WHF定义还包括，在特定的心肌病中，炎性心肌病作为一个独特的实体，定义为与心功能障碍相关的心肌炎。特发性、自身免疫性和感染性形式的炎症性心肌病被确认。病毒性心肌病被定义为病毒在扩张的心脏中持续存在。它可能伴有心肌炎症，然后被称为炎症性病毒性心肌病（或病毒性心肌炎伴心脏肥大）。如果在扩张的心脏活检中未观察到炎症（< 14淋巴细胞和巨噬细胞/mm(2)），则应根据WHF工作组的建议，使用病毒性心肌病或DCM病毒持续性这一术语。在德国心力衰竭网络中，作者的工作假设是，DCM与其他假定的自身免疫性疾病具有相同的遗传风险因素，因此，相同的多个基因与环境因素结合导致许多不同的自身免疫性疾病，包括DCM。因此，作者的主要目标是获得DCM患者的流行病学资料，包括该疾病的感染和炎症病因。间接证据指出病毒性心肌炎在DCM的病因学中起主要作用。病毒遗传物质在DCM患者心肌中的普遍存在提供了最令人信服的证据，但因果关系的证据仍然缺乏。此外，在许多研究中描述了自身免疫反应，表明它们是一个重要的病因。然而，关于两种机制都起作用的患者比例的数据仍然缺失。在相当大比例的DCM患者中，自身免疫的关键作用是由器官特异性自身抗体、炎症浸润和促炎细胞毒性细胞因子的存在所支持的。此外，大约20-30%的DCM病例被描述为家族性发生，在无症状左心室增大的一级亲属中存在自身抗体和异常细胞因子谱。这表明在疾病发展的早期参与了体液和细胞免疫的破坏。在其他自身免疫性疾病中也有类似的体液和细胞免疫失调模式。有相当多的证据表明，遗传因素在DCM的发病机制中起着重要作用，无论是作为对环境因素的易感性的贡献者，还是作为表征该疾病表型表达的功能和结构变化的决定因素。然而，尚不清楚对免疫介导的心肌损伤的易感性是否反映了其他自身免疫性疾病共有的遗传危险因素的存在。初步调查表明，这是事实，因为DCM患者的一级亲属中除DCM外的自身免疫性疾病的频率更高，包括青少年糖尿病、类风湿关节炎、甲状腺炎、牛皮癣和哮喘。遗传风险的性质尚不确定，可能涉及主要组织相容性（MHC）位点以及其他易感位点的基因。因此，作者开始了他们的研究，在DCM患者外周血中寻找MHC 2类DO多态性，同时通过使用微阵列分析有关炎症和自身免疫性疾病的基因来寻找新的有趣的易感位点。通过这种方法，对DCM患者中其他自身免疫性疾病的家族聚类和遗传易感性有了新的认识。
Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis With cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing. A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases,with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease. Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk factors shared by other autoimmune diseases. Preliminary investigations suggest, that this is the case, because the frequency of autoimmune disorders other than DCM was higher in first-degree relatives of the subjects with DCM including juvenile diabetes, rheumatoid arthritis, thyroiditis, psoriasis, and asthma. The nature of the genetic risk is undetermined and probably involves genes in the major histocompatibility (MHC) locus as well as other susceptibility loci.Therefore, the authors started their investigation wih the search for MHC class 2 DO polymorphisms in the peripheral blood of patients with DCM in parallel to the search for new interesting susceptibility loci by the use of the microarray analysis regarding genes responsible for inflammatory and autoimmune diseases. By this approach a new insight in the familial clustering of other autoimmune diseases in patients with DCM and in genetic predisposition can be expected.