title: Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies.
abstract: The development of an animal model for studying the pathogenesis of pemphigus vulgaris (PV) has been hampered by the unavailability of the purified full-length autoantigen desmoglein 3 (Dsg 3).Therefore, we expressed Dsg 3 using a baculovirus expressed system. The expressed protein was identified as Dgs 3 by its reactivity with a pan-cadherin anti-serum, an anti-serum to a Dsg 3 synthetic peptide, or patient serum, and by amino-terminal sequencing. Carbohydrate analysis showed that recombinant Dsg 3 was glycosylated. While a majority of the recombinant protein was cell associated, by immunoprecipitation, some Dsg 3 was demonstrated in the medium. The Dgs 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 monkeys esophagus by indirect immunofluorescence. Moreover, these antibodies induced PV-like blisters in neonatal mice and weakly bound perilesional epidermis. Availability of large quantities of relatively pure Dsg 3 should now facilitate studies aimed at understanding Dsg 3 structure and pathogenesis of PV, with implications for developing specific immunotherapies.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, 77555-1019, USA.
authors.forename: O M
authors.initials: OM
authors.lastname: Memar
authors.forename: S
authors.initials: S
authors.lastname: Rajaraman
authors.forename: R
authors.initials: R
authors.lastname: Thotakura
authors.forename: S K
authors.initials: SK
authors.lastname: Tyring
authors.forename: J L
authors.initials: JL
authors.lastname: Fan
authors.forename: G S
authors.initials: GS
authors.lastname: Seetharamaiah
authors.forename: A
authors.initials: A
authors.lastname: Lopez
authors.forename: R E
authors.initials: RE
authors.lastname: Jordon
authors.forename: B S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D015820:Cadherins / Q000096:biosynthesis / Q000276:immunology*; D051184:Desmoglein 3; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007313:Insecta / Q000166:cytology; D051379:Mice; D010392:Pemphigus / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000906:Antibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D000939:Epitopes; D011994:Recombinant Proteins