ULTRASTRUCTURAL-LOCALIZATION OF CELL JUNCTIONAL COMPONENTS (DESMOGLEIN, PLAKOGLOBIN, E-CADHERIN, AND BETA-CATENIN) IN HAILEY-HAILEY-DISEASE, DARIERS-DISEASE, AND PEMPHIGUS-VULGARIS

The distribution of desmoglein, plakoglobin, E-cadherin, and beta-cate nin in the peri-lesional and lesional skin of Hailey-Hailey disease, D arier's disease, and pemphigus vulgaris was examined by immunoelectron microscopy. In the peri-lesional skin, the immunolabeling of these de smosomal components was localized to desmosomes. Adherens junction-ass ociated E-cadherin and beta-catenin were at the cell periphery, exclud ing desmosomes. The labeling pattern was similar among these diseases, but the labeling intensity particularly that of plakoglobin in Hailey -Hailey disease and Darier's disease, was less than that of normal con trols, suggesting that these glycoproteins are quantitatively less con centrated in the normal epidermis of these inherited diseases. In the acantholytic cells of Hailey-Hailey disease and Darier's disease the i mmunolabeling of the components of desmosomes was diffusely distribute d in the cytoplasms, whereas that of adherens junction was mostly at t he cell periphery and partly diffusely in the cytoplasm. In contrast, desmosomes of detaching keratinocytes in pemphigus vulgaris still show ed the labeling of desmoglein and plakoglobin. These findings suggest that the inherited acantholytic diseases, i.e., Hailey-Hailey disease and Darier's disease have a different pathogenesis from that of autoim mune acantholysis in pemphigus vulgaris: The intracellular components of desmosomes may primarily be disrupted in the genetic acantholytic d iseases in the initial stages of acantholysis. Several unsolved questi ons in the previous light microscopic immunofluorescence studies using the same antibodies are now answered: I) the diffusion of desmosomal proteins is not due to the internalization of desmosomes, 2) intracell ular components of adherens junction are also finally dissolved, 3) di ffuse cytoplasmic immunofluorescence patterns of desmosomal components could be explained by immunoelectron microscopy as those attached to cell membrane and trapped in tonofilament aggregates.