Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions

Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (P F) are caused by a dissociation of desmosomes mediated by autoantibodies ag ainst desmoglein (Dsg) 3 and Dsg 1, respectively, The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PE which corres ponds to the distribution of target antigens in the epidermis: there is a m ore prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysi s, we studied the alterations of the desmosomal components and the expressi on pattern of Dsg isoforms in the lesional and perilesional epidermis of pe mphigus patients. The results demonstrated an internalization of the desmos omes in the lower epidermis of PV, PF and pemphigus vegetans, A similar phe nomenon was induced in monolayers of keratinocytes cultured with PV sera. H owever, little change was observed in E-cadherin expression until acantholy sis became manifest. This internalization occurred prior to overt acantholy sis, and was frequently associated with the induction of Dsg 2 expression i n the basilar or lower layers of the epidermis, These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, whic h might be related to the characteristic acantholytic patterns: the supraba silar layer in PV and the upper epidermis in PF.