Kühl U, Daun B, Seeberg B, Schultheiss H P, Strauer B E
Medizinische Klinik für Kardiologie, Pulmonologie und Angiologie, Universität Düsseldorf.
Herz. 1992 Apr;17(2):97-106.
Experimental and clinical data suggest a relationship between myocarditis and dilated cardiomyopathy. One postulated pathomechanism is a viral infection triggering a host response with autoimmune features directed against the heart, resulting in an initial myocarditis which is followed by a dilated cardiomyopathy. Until now, the importance of an undetected myocarditis as an etiological factor in the pathogenesis of idiopathic cardiomyopathy is unknown. This investigation was undertaken to determine the frequency of lymphocytic infiltrations in endomyocardial biopsies of patients with dilated cardiomyopathy by immunohistological methods and to analyze T lymphocytic subsets and other immunological features in order to search for possible relationships between immunohistological-documented myocarditis and dilated cardiomyopathy. In our study, 48 of 130 biopsies (37%) from patients with clinically proven dilated cardiomyopathy contained lymphocytic infiltrates when stained by the immunoperoxidase method with lymphocyte surface markers (Table 1). 23% (n = 30) of these biopsies contained more than 2.0 (range: 2.0 to 13.8) T lymphocytes per high power light microscopy field (x 400), in 14% (n = 18) 1.5 to 2.0 cells/HPH were seen (Table 2). 82 biopsies (63%) with less than 0.8 cells/HPF were regarded as negative (dilated cardiomyopathy). By histological analysis, only seven cases (5%) were classified as borderline myocarditis by conventional histological evaluation according to the Dallas classification. In the other patients, our results were consistent with the clinical diagnosis of dilated cardiomyopathy (Table 1). 71% of biopsies with lymphocytic infiltrates contained activated T cells when analysed with activation markers in serial sections (Table 2). Activated macrophages were seen in 52% of biopsies with T cell infiltrations, but only in 31% of tissues containing normal numbers of lymphocytes (Table 2). In biopsy specimens with lymphocytic infiltrates HLA-class I and II antigen expression was increased. An enhanced HLA-DR antigen staining was seen in 80% on interstitial cells and vascular endothelium while HLA class I was found at an increased level in 67% (Table 3). In negative biopsies, an enhanced class I staining was seen in only 14%, class II in 30%. Because of the specific identification of lymphocytes by immunocytochemical methods, lymphocytic infiltrates are easily detected, even if the infiltrate is sparse or focal (Figure 1). The considerable interobserver variability in the quantitation of lymphocyte counts, which is a main problem in hematoxylin and eosin stained sections is negligible when lymphocyte quantitation is performed by immunoperoxidase staining. Thus, our data indicate that in about 37% of patients with clinical suspected idiopathic cardiomyopathy an ongoing or reactivated myocarditic process is involved.(ABSTRACT TRUNCATED AT 400 WORDS)
实验和临床数据表明心肌炎与扩张型心肌病之间存在关联。一种假定的发病机制是病毒感染引发具有针对心脏的自身免疫特征的宿主反应,导致初始心肌炎,随后发展为扩张型心肌病。到目前为止,未被检测到的心肌炎作为特发性心肌病发病机制中的病因因素的重要性尚不清楚。本研究旨在通过免疫组织学方法确定扩张型心肌病患者心内膜活检中淋巴细胞浸润的频率,并分析T淋巴细胞亚群和其他免疫特征,以寻找免疫组织学证实的心肌炎与扩张型心肌病之间的可能关系。在我们的研究中,130例经临床证实为扩张型心肌病患者的活检标本中,48例(37%)在用淋巴细胞表面标志物进行免疫过氧化物酶染色时含有淋巴细胞浸润(表1)。这些活检标本中,23%(n = 30)在高倍光学显微镜视野(×400)下每视野含有超过2.0个(范围:2.0至13.8个)T淋巴细胞,14%(n = 18)每视野可见1.5至2.0个细胞(表2)。82例(63%)每高倍视野细胞数少于0.8个的活检标本被视为阴性(扩张型心肌病)。通过组织学分析,根据达拉斯分类,只有7例(5%)经传统组织学评估被归类为边缘性心肌炎。在其他患者中,我们的结果与扩张型心肌病的临床诊断一致(表1)。当用连续切片中的激活标志物分析时,71%有淋巴细胞浸润的活检标本含有活化T细胞(表2)。在有T细胞浸润的活检标本中,52%可见活化巨噬细胞,但在淋巴细胞数量正常的组织中仅31%可见(表2)。在有淋巴细胞浸润的活检标本中,HLA - I类和II类抗原表达增加。80%的间质细胞和血管内皮细胞可见增强的HLA - DR抗原染色,而67%的标本中HLA - I类抗原水平升高(表3)。在阴性活检标本中,仅14%可见I类染色增强,30%可见II类染色增强。由于通过免疫细胞化学方法能特异性识别淋巴细胞,即使浸润稀疏或呈局灶性,淋巴细胞浸润也很容易被检测到(图1)。当通过免疫过氧化物酶染色进行淋巴细胞定量时,苏木精和伊红染色切片中淋巴细胞计数的观察者间差异这一主要问题可忽略不计。因此,我们的数据表明,在约37%临床疑似特发性心肌病的患者中,存在正在进行或重新激活的心肌炎症过程。(摘要截短至400字)