Masashi Harada

Desmosomal dissolution in Grover's disease, Hailey‐Hailey's disease and Darier's disease

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non‐immune acantholytic diseases; specifically, four cases of Grovers disease (GD), one case of Hailey‐Haileys disease (HMD) and one case of Dariers disease (DD), and these were compared to two cases of immune‐mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot‐like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.

Epithelial cell membrane specific, novel monoclonal antibody KA-1.

In order to develop a novel monoclonal antibody reacting with the cell membrane protein which could be a receptor for cell growth, differentiation or an adhesion molecule, keratinocytes from psoriatic epidermis and A-431 cell line were used to immunize BALB/c mice. A monoclonal antibody, KA-1 was developed. KA-1 reacts with the cell membranes of the whole epidermis with the exception of the stratum corneum cells and the basal cell membrane in contact with the basement membrane. In electron microscopy, the antigenic site was located on the surface of the microvilli of the cultured keratinocytes, especially at the contact area with another villi, the cell membrane or collagen. The antigenic protein was a 44-kDa protein which was different from E-cadherin in both molecular weight and cross-reactivity.