Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier's disease

Background: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pem phigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. R ecently, mutations in the genes coding Ca2+ pumps leads to inherited bliste ring diseases, Hailey-Hailey disease (HHD) and Darier's disease (DD). Cadhe rins are a family of Ca2+-dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been full y clarified, abnormal expression of cadherins caused by altered Ca2+ concen tration due to the binding of autoantibodies to cell surface or by mutation s in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis o f these atuoimmune and inherited blistering diseases. The purpose of the pr esent study was to determine whether altered P-cadherin expression is prese nt in these diseases. Method: Distribution patterns of P-cadherin in skin specimens hem patients with PV (n=2), PF (n=2), Ill-ID (n=4) and DD (n=3), were examined with conf ocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 an d NCC-CAD-299. Results: In normal control skin, P-cadherin expression was restricted to th e basal layer. In contrast, positive immunostaining of P-cadherin was obser ved not only in the basal cells, but also in the suprabasal cells in lesion al skin of all the acantholytic diseases. Conclusions: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, I-II-ID and DD. Upregulation of P-cadherin may be involve d in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases.