Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic

Masayuki Amagai, S. Kárpáti, Ronald Prussick, Vera Klaus-Kovtun, John R. Stanley

Research output: Contribution to journalArticle

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Abstract

Complementary DNA cloning of the 130-kD pemphigus vulgaris (PV) autoantigen (PVA) has indicated that it is a member of the cadherin family of Ca2+-dependent cell adhesion molecules. By homology with typical cadherins, PVA has five extracellular domains (EC1 through EC5). To localize immunogenic domains and to determine whether antibodies against them might be pathogenic, we produced β-galactosidase fusion proteins with cDNA encoding different portions of the extracellular domains of PVA (EC1-2, EC3-5, and each individual domain). Immunoblot analysis of these fusion proteins with 23 PV patients' sera demonstrated that major immunogenic regions of PVA are located on the EC1, EC2, and EC4 domains. IgG was affinity-purified from PV sera on fusion proteins representing the amino (EC1-2) and carboxy (EC3-5) terminus of the extracellular PVA, and injected into neonatal mice. PV IgG affinity-purified on the EC1-2 fusion protein caused suprabasilar acantholysis, the typical histological finding of PV, but IgG affinity-purified on the EC3-5 fusion protein or β-galactosidase alone did not. These results indicate that at least one pathogenic epitope, which is sufficient to cause suprabasilar acantholysis in neonatal mice, is located on the amino-terminal region of PVA, an area thought to be important in cadherin homophilic adhesion.

Original languageEnglish
Pages (from-to)919-926
Number of pages8
JournalJournal of Clinical Investigation
Volume90
Issue number3
Publication statusPublished - 1992

Fingerprint

Pemphigus
Autoantigens
Cadherins
Autoantibodies
Antigens
Acantholysis
Galactosidases
Immunoglobulin G
Proteins
Complementary DNA
Cell Adhesion Molecules
Serum
Organism Cloning
Epitopes
Antibodies

Keywords

  • Acantholysis
  • Autoimmunity
  • Cell adhesion
  • Desmosome
  • Immunogenic domain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. / Amagai, Masayuki; Kárpáti, S.; Prussick, Ronald; Klaus-Kovtun, Vera; Stanley, John R.

In: Journal of Clinical Investigation, Vol. 90, No. 3, 1992, p. 919-926.

Research output: Contribution to journalArticle

Amagai, Masayuki ; Kárpáti, S. ; Prussick, Ronald ; Klaus-Kovtun, Vera ; Stanley, John R. / Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 3. pp. 919-926.
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