Differences in the expression of pemphigus antigens during epidermal differentiation

Epidermal desmogleins with molecular weights of 130/140 kDa (Dsg3 or PVA) and 150/160 kDa (Dsg1 or DGI) are recognized by autoantibodies from patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF), respectively. In order to understand the histogenesis of both types of pemphigus, we studied the expression patterns of Dsg1 and Dsg3 during stratification of cultured keratinocytes. Monolayers of cultured normal human keratinocytes demonstrated uniform intercellular staining with PV sera. The staining pattern was distinct from the focal staining with PF sera observed only in the stratified areas. Both Dsg1 and Dsg3 proteins and their mRNA were expressed by the monolayers, whereas no production of Dsg2 (HDGC) mRNA was found. The relative ratio of Dsg3 to the total desmogleins, as determined by density on immunoblotting, decreased as the cultured keratinocytes stratified. In the completely stratified keratinocytes cultured on collagen membrane, Dsg1 became predominant, with subsequent reduction of PV antigen expression. The relative decrease of Dsg3 (PVA) during epidermal differentiation might be responsible for the induction of suprabasal acantholysis in PV.