Inappropriate major histocompatibility complex expression on cardiac tissue in dilated cardiomyopathy. Relevance for autoimmunity?

Abstract

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 < 0.001 and 11 63 , P < 0.001 respectively). In all the DCM biopsies examined there was a hierarchy of Class II subloci product expression (DR > DP > 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.