Herskowitz A, Ahmed-Ansari A, Neumann D A, Beschorner W E, Rose N R, Soule L M, Burek C L, Sell K W, Baughman K L
Department of Immunology and Infectious Diseases, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland.
J Am Coll Cardiol. 1990 Mar 1;15(3):624-32. doi: 10.1016/0735-1097(90)90637-5.
The histologic diagnosis of active myocarditis is frequently difficult to establish. A nonhistologic marker of immune activation would be clinically useful in identifying cases of immune-mediated myocarditis. A viral etiology with subsequent autoimmunity to cardiac antigens has been implicated in human myocarditis. Because autoimmunity and viral disease are commonly associated with increased expression of major histocompatibility complex (MHC) antigens on targeted tissue, we examined endomyocardial biopsy samples from patients with active myocarditis for abnormal levels of MHC antigen expression. Thirteen patients with active myocarditis and eight control patients with other well-defined cardiac diagnoses (coronary disease, amyloidosis or neoplasm) were studied. A sensitive radioimmunoassay was developed that utilized monoclonal antibodies to human MHC class I and class II antigens in order to quantitate the expression of both of these antigens within each biopsy. Abnormal MHC class I and class II antigen expression was present in 11 of 13 myocarditis specimens and 1 of 8 control samples (specificity 88%, sensitivity 84.6%). Active myocarditis samples had approximately a 10-fold increase in MHC class I and class II expression. Immunoperoxidase staining localized abnormal MHC expression primarily within microvascular endothelium and along myocyte surfaces (11 of 13). This study is the first to demonstrate a marked increase in major histocompatibility complex antigen expression within the myocardium of patients with active myocarditis. The identification of abnormal histocompatibility antigen expression within an endomyocardial biopsy may prove a useful adjunct to the histologic diagnosis of myocarditis.
活动性心肌炎的组织学诊断常常难以确立。免疫激活的非组织学标志物在识别免疫介导性心肌炎病例方面具有临床实用性。病毒病因随后引发对心脏抗原的自身免疫反应被认为与人类心肌炎有关。由于自身免疫和病毒疾病通常与靶组织上主要组织相容性复合体（MHC）抗原表达增加相关，我们检查了活动性心肌炎患者的心内膜活检样本中MHC抗原表达水平是否异常。研究了13例活动性心肌炎患者和8例患有其他明确心脏疾病（冠心病、淀粉样变性或肿瘤）的对照患者。开发了一种灵敏的放射免疫测定法，该方法利用针对人类MHC I类和II类抗原的单克隆抗体来定量每个活检样本中这两种抗原的表达。13例心肌炎标本中有11例以及8例对照样本中有1例出现MHC I类和II类抗原表达异常（特异性88%，敏感性84.6%）。活动性心肌炎样本中MHC I类和II类表达大约增加了10倍。免疫过氧化物酶染色显示异常的MHC表达主要位于微血管内皮细胞内以及心肌细胞表面（13例中有11例）。本研究首次证明活动性心肌炎患者心肌内主要组织相容性复合体抗原表达显著增加。在心内膜活检中识别出异常的组织相容性抗原表达可能证明是心肌炎组织学诊断的有用辅助手段。
