RECOMBINANT DESMOGLEIN-3 HAS THE NECESSARY EPITOPES TO ADSORB AND INDUCE BLISTER-CAUSING ANTIBODIES

The development of an animal model for studying the pathogenesis of pe mphigus vulgaris (PV) has been hampered by the unavailability of the p urified full-length autoantigen desmoglein 3 (Dsg 3). Therefore, we ex pressed Dsg 3 using a baculovirus expression system, The expressed pro tein was identified as Dsg 3 by its reactivity with a pan-cadherin ant i-serum, an anti-serum to a Dsg 3 synthetic peptide, or patient serum, and by amino-terminal sequencing. Carbohydrate analysis showed that r ecombinant Dsg 3 was glycosylated. While a majority of the recombinant protein was cell associated, by immunoprecipitation, some Dsg 3 was d emonstrated in the medium. The Dsg 3 could adsorb out blister-causing antibodies from patient sera. Rabbit anti-Dsg 3 antibodies induced by the recombinant Dsg 3 showed specific binding to intercellular spaces of monkey esophagus by indirect immunofluorescence. Moreover, these an tibodies induced PV-like blisters in neonatal mice and weakly bound pe rilesional epidermis. Availability of large quantities of relatively p ure Dsg 3 should now facilitate studies aimed at understanding Dsg 3 s tructure and pathogenesis of PV, with implications for developing spec ific immunotherapies.