PEMPHIGUS-VULGARIS ANTIGEN (DESMOGLEIN-3) IS LOCALIZED IN THE LOWER EPIDERMIS, THE SITE OF BLISTER FORMATION IN PATIENTS

In patients with pemphigus vulgaris, autoantibodies against the desmos omal glycoprotein desmoglein 3 (Dsg3) cause blisters due to loss of ke ratinocyte cell-cell adhesion in the basal and immediate suprabasal la yer of the deeper epidermis, leaving the superficial epidermis intact. Autoantibodies from these patients, however, usually bind to the cell surface of keratinocytes throughout the entire epidermis, as determin ed by indirect immunofluorescence. To explain this apparent paradox, w e immunoadsorbed pemphigus vulgaris sera with the extracellular domain s of Dsg3 and desmoglein 1 (Dsg1) produced by insect cells infected wi th recombinant baculovirus. When adsorbed with extracellular domains o f both Dsg3 and Dsg1, these sera no longer stained epidermis, demonstr ating that most, if not all, of their cell surface reactivity can be a ttributed to antibodies against the extracellular domains of these des mogleins. Adsorption with only the Dsg1 extracellular domain left anti bodies that stained only the basal and immediate suprabasal layers of the epidermis and immunoprecipitated only Dsg3, not Dsg1, from extract s of cultured cells synthesizing these molecules, In contrast, adsorpt ion with only the Dsg3 extracellular domain left antibodies that stain ed only the more superficial epidermis and immunoprecipitated only Dsg 1. These data localize Dsg3 exactly Co the area in the epidermis where blisters occur in pemphigus vulgaris.