Caforio A L, Stewart J T, Bonifacio E, Burke M, Davies M J, McKenna W J, Bottazzo G F
Department of Cardiological Sciences, St George's Hospital Medical School, London, UK.
J Autoimmun. 1990 Apr;3(2):187-200. doi: 10.1016/0896-8411(90)90140-n.
The inappropriate expression of major histocompatibility complex (MHC) molecules on epithelial and endothelial cells is a recognized marker of autoimmune disease. An autoimmune pathogenesis has been suspected in dilated cardiomyopathy (DCM). In the normal heart, MHC products are usually not detectable on myocytes using immunochemical techniques. MHC molecule expression has not, however, been assessed on cardiac endothelial cells. The aim of this study was to investigate possible autoimmune phenomena and MHC molecule expression in fresh endomyocardial biopsies from 29 patients with DCM. These were compared with those observed in surgical specimens from 63 patients with other acquired cardiac disease and from 22 with congenital heart disease (CHD) as normal controls. Conventional immunofluorescence (IFL) with monoclonal antibodies (MoAbs) to lymphocyte and macrophage markers and to MHC molecules was employed, and double IFL with antiserum to human Factor VIII was used for the identification of endothelial cells. Myocytes did not express MHC molecules in either DCM or controls. In normal hearts, Class II molecules were detected on endothelial and endocardial cells in only a few cases (3/22 and 2/22 respectively). By contrast, endothelial and endocardial cells inappropriately expressed Class II in a high proportion of DCM patients (28/29 and 22/29) but less frequently in other acquired cardiac diseases (19/63, P less than 0.001 and 11/63, P less than 0.001 respectively). In all the DCM biopsies examined there was a hierarchy of Class II subloci product expression (DR greater than DP greater than DQ); lymphocytic infiltration was a rare finding and macrophages/dendritic cells were not prominent. The finding of inappropriate MHC Class II molecule expression on cardiac endothelial and on endocardial cells suggests a possible pathogenic role for these cells in the initiation and/or perpetuation of DCM.
上皮细胞和内皮细胞上主要组织相容性复合体（MHC）分子的不适当表达是自身免疫性疾病的一个公认标志。扩张型心肌病（DCM）一直被怀疑存在自身免疫发病机制。在正常心脏中，使用免疫化学技术通常在心肌细胞上检测不到MHC产物。然而，尚未对心脏内皮细胞的MHC分子表达进行评估。本研究的目的是调查29例DCM患者新鲜心内膜活检中可能的自身免疫现象和MHC分子表达情况。将这些结果与63例其他获得性心脏病患者和22例先天性心脏病（CHD）患者的手术标本作为正常对照进行比较。采用针对淋巴细胞和巨噬细胞标志物以及MHC分子的单克隆抗体（MoAbs）进行常规免疫荧光（IFL）检测，并使用抗人因子VIII抗血清进行双重IFL检测以鉴定内皮细胞。在DCM组和对照组中，心肌细胞均未表达MHC分子。在正常心脏中，仅在少数情况下（分别为3/22和2/22）在内皮细胞和心内膜细胞上检测到II类分子。相比之下，在高比例的DCM患者中（28/29和22/29），内皮细胞和心内膜细胞不适当表达II类分子，但在其他获得性心脏病中表达频率较低（分别为19/63，P<0.001和11/63，P<0.001）。在所有检查的DCM活检标本中，II类基因座产物表达存在层次结构（DR>DQ）；淋巴细胞浸润罕见，巨噬细胞/树突状细胞不突出。心脏内皮细胞和心内膜细胞上不适当的MHC II类分子表达的发现表明这些细胞在DCM的起始和/或持续存在中可能具有致病作用。
