Induction of Blister-Causing Antibodies by a Recombinant Full-Length, but Not the Extracellular, Domain of the Pemphigus Vulgaris Antigen (Desmoglein 3)

Omeed Memar, Burgess Christensen, Srinivasan Rajaraman, Randall Goldblum, Stephen K. Tyring, Miriam M. Brysk, Daniel J. McCormick, Haissam El Zaim, Ji Lao Fan, Bellur S. Prabhakar

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Pemphigus vulgaris (PV) is mediated by autoantibodies to desmoglein 3, the pemphigus vulgaris antigen (PVA). PVA and an extracellular domain of PVA-Ig fusion protein (PV-Ig) can completely adsorb the blister-causing Abs from PV patient sera, suggesting that the extracellular segment of PVA might be sufficient to induce pathogenic Abs. To test this, we immunized rabbits with either PVA or its extracellular domain (EPVA) expressed in insect cells in our laboratory. When Igs were passively transferred from these rabbits into neonatal mice, anti-PVA, but not the anti-EPVA, induced blisters. To understand the basis for their differential pathogenic effects, we examined the properties of these sera. Both sera showed comparable ELISA titers and indirect immunofluorescence reactivity against monkey esophagus, a source of native PVA. Moreover, EPVA, like PVA adsorbed blister-causing Abs from sera of PV patients and rabbits immunized with PVA. In contrast, when IgC preparations were incubated with fura-2-AM (acetyloxymethyl ester)-loaded human keratinocytes in culture, only IgG from anti-PVA serum induced intracellular calcium mobilization. These data showed that PVA but not EPVA can elicit Abs that induce blisters in neonatal mice and mediate intracellular signaling through calcium mobilization.

Original languageEnglish (US)
Pages (from-to)3171-3177
Number of pages7
JournalJournal of Immunology
Volume157
Issue number7
StatePublished - Oct 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Induction of Blister-Causing Antibodies by a Recombinant Full-Length, but Not the Extracellular, Domain of the Pemphigus Vulgaris Antigen (Desmoglein 3)'. Together they form a unique fingerprint.

  • Cite this

    Memar, O., Christensen, B., Rajaraman, S., Goldblum, R., Tyring, S. K., Brysk, M. M., McCormick, D. J., El Zaim, H., Fan, J. L., & Prabhakar, B. S. (1996). Induction of Blister-Causing Antibodies by a Recombinant Full-Length, but Not the Extracellular, Domain of the Pemphigus Vulgaris Antigen (Desmoglein 3). Journal of Immunology, 157(7), 3171-3177.