Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus

Masayuki Amagai, Takashi Hashimoto, Nobuyoshi Shimizu, Takeji Nishikawa

Research output: Contribution to journalArticle

276 Citations (Scopus)

Abstract

Pemphigus vulgaris (PV) is an autoimmune blistering disease, in which autoantibodies against PV antigen (PVA or Dsg3) play a pathogenic role in inducing blister formation. Bacterial fusion proteins of PVA failed to absorb pathogenic autoantibodies from PV patients' sera probably because they did not represent the proper conformation. Therefore, a chimeric protein, PVIg, consisting of the whole extracellular domain of PVA and the constant region of human IgG1, was produced in either in COS7 or in insect Sf9 eucaryotic cells. Both PVIg-COS7 and PVIg-Sf9 were recognized by all of the 35 PV sera tested, but not by any of 10 pemphigus foliaceus (PF), 16 Brazilian PF, 10 bullous pemphigoid, or five normal control sera. Incubation of PV patients' sera with PVIg-Sf9 removed heterogeneous autoantibodies and significantly reduced their immunofluorescence titers on normal human epidermis, although PVIg-Sf9 did not affect the titers of PF sera at all. Furthermore, PVIg-Sf9 absorbed pathogenic autoantibodies from patients' sera and prevented gross blister formation in a neonatal mouse model for pemphigus. These results indicate that this baculovirus product has the proper conformation of the authentic PVA and that its conformation is important in pathogenicity of pemphigus.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalJournal of Clinical Investigation
Volume94
Issue number1
Publication statusPublished - 1994 Jul

Fingerprint

Pemphigus
Baculoviridae
Autoantibodies
Antigens
Serum
Blister
Sf9 Cells
Bullous Pemphigoid
Bacterial Proteins
Epidermis
Autoimmune Diseases
Fluorescent Antibody Technique
Virulence
Insects
Immunoglobulin G

Keywords

  • autoimmune disease
  • cadherin
  • desmoglein
  • neonatal mouse model
  • therapy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus. / Amagai, Masayuki; Hashimoto, Takashi; Shimizu, Nobuyoshi; Nishikawa, Takeji.

In: Journal of Clinical Investigation, Vol. 94, No. 1, 07.1994, p. 59-67.

Research output: Contribution to journalArticle

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