In order to clarify the pathomechanism of
acantholysis in
Hailey-Hailey disease (HHD) and
Darier's disease (DD), the distribution of desmosomal and adherens junction-associated
proteins was studied in the skin of patients with HHD (n = 4) and DD (n = 3). Domain-specific
antibodies were used to determine the cellular localization of the desmosomal transmembrane
glycoproteins (
desmogleins 1 and 3 and
desmocollin), desmosomal plaque
proteins (
desmoplakin,
plakophilin and
plakoglobin) and adherens junction-associated
proteins (
E-cadherin,
alpha-catenin,
beta-catenin and actin). A significant difference in staining patterns between intra- and extracellular domains of
desmosomal cadherins and
E-cadherin was demonstrated in acantholytic cells in both HHD and DD, but not in those in
pemphigus vulgaris and
pemphigus foliaceus samples used as controls. In acantholytic cells in HHD and DD,
antibodies against attachment plaque
proteins and intracellular
epitopes of
desmosomal cadherins exhibited diffuse cytoplasmic staining, whereas markedly reduced staining was observed with
antibodies against extracellular
epitopes of the
desmogleins. Similarly, membrane staining of an intracellular
epitope of
E-cadherin was preserved, while immunoreactivity of an extracellular
epitope of
E-cadherin was destroyed. While the DD gene has been identified as ATP2A2, the gene for HHD has not been clarified. The dissociation of intra- and extracellular domains of desmosomal
cadherin and
E-cadherin is characteristic of the acantholytic cells in HHD and DD, and not of
pemphigus. This common phenomenon in HHD and DD might be closely related to the pathophysiological mechanisms in both conditions.