Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies

Omeed M. Memar, Srinivasan Rajaraman, Rao Thotakura, Stephen K. Tyring, Ji Lao Fan, Gattadahalli S. Seetharamaiah, Angel Lopez, Robert E. Jordon, Bellur S. Prabhakar

Research output: Contribution to journalArticle

25 Scopus citations

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 expression system. The expressed protein was identified as Dsg 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 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 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.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalJournal of Investigative Dermatology
Volume106
Issue number2
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • Acantholysis
  • Autoimmunity
  • Bculovirus
  • Pemphigus vulgaris

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Memar, O. M., Rajaraman, S., Thotakura, R., Tyring, S. K., Fan, J. L., Seetharamaiah, G. S., Lopez, A., Jordon, R. E., & Prabhakar, B. S. (1996). Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies. Journal of Investigative Dermatology, 106(2), 261-268. https://doi.org/10.1111/1523-1747.ep12340663