ANTIBODIES AGAINST DESMOGLEIN 3 (PEMPHIGUS-VULGARIS ANTIGEN) ARE PRESENT IN SERA FROM PATIENTS WITH PARANEOPLASTIC PEMPHIGUS AND CAUSE ACANTHOLYSIS IN-VIVO IN NEONATAL MICE

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease tha t occurs in association with underlying neoplasms. Patients with PNP d evelop characteristic IgG autoantibodies directed against multiple ant igens, most of which have been identified as cytoplasmic proteins of t he plakin family (desmoplakin I, II, BPAG1, envoplakin, and periplakin ). This study identified cell surface target antigens of PNP. We focus ed on desmoglein (Dsg) 3 and Dsg1, the autoantigens of pemphigus vulga ris and pemphigus foliaceus. ELISA using baculovirus-expressed recombi nant Dsgs (rDsg3, rDsg1) has revealed that 25 out of 25 PNP sera teste d were positive against Dsg3 and 16 of 25 were positive against Dsg1, All of 12 PNP sera tested immunoprecipitated Dsg3. Removal of anti-Dsg 3 autoantibodies by immunoadsorption was sufficient to eliminate the a bility of PNP sera to induce cutaneous blisters in neonatal mice in vi vo. Furthermore, anti-Dsg3-specific antibodies that were affinity puri fied from PNP sera were proven to be pathogenic and caused blisters in neonatal mice. These findings indicate that Dsg3 and Dsg1 are the cel l surface target antigens in PNP and that IgG autoantibodies against D sg3 in PNP sera play a pathogenic role in inducing loss of cell adhesi on of keratinocytes and causing blister formation.