Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus

Takashi Hashimoto, Chie Kiyokawa, Osamu Mori, Minoru Miyasato, Martyn A J Chidgey, David R. Garrod, Yasushi Kobayashi, Koji Komori, Ken Ishii, Masayuki Amagai, Takeji Nishikawa

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169 Citations (Scopus)

Abstract

IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.

Original languageEnglish
Pages (from-to)127-131
Number of pages5
JournalJournal of Investigative Dermatology
Volume109
Issue number2
Publication statusPublished - 1997

Fingerprint

Desmocollins
Vesiculobullous Skin Diseases
Pemphigus
Autoantigens
Immunoglobulin A
Skin Diseases
Conformations
Epitopes
Desmogleins
Cells
Keratinocytes
Immunoblotting
Autoantibodies
Fluorescent Antibody Technique
Skin

Keywords

  • Autoimmune bullous disease
  • Desmosome
  • Keratinocyte
  • Mammalian cell transfection

ASJC Scopus subject areas

  • Dermatology

Cite this

Hashimoto, T., Kiyokawa, C., Mori, O., Miyasato, M., Chidgey, M. A. J., Garrod, D. R., ... Nishikawa, T. (1997). Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. Journal of Investigative Dermatology, 109(2), 127-131.

Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. / Hashimoto, Takashi; Kiyokawa, Chie; Mori, Osamu; Miyasato, Minoru; Chidgey, Martyn A J; Garrod, David R.; Kobayashi, Yasushi; Komori, Koji; Ishii, Ken; Amagai, Masayuki; Nishikawa, Takeji.

In: Journal of Investigative Dermatology, Vol. 109, No. 2, 1997, p. 127-131.

Research output: Contribution to journalArticle

Hashimoto, T, Kiyokawa, C, Mori, O, Miyasato, M, Chidgey, MAJ, Garrod, DR, Kobayashi, Y, Komori, K, Ishii, K, Amagai, M & Nishikawa, T 1997, 'Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus', Journal of Investigative Dermatology, vol. 109, no. 2, pp. 127-131.
Hashimoto T, Kiyokawa C, Mori O, Miyasato M, Chidgey MAJ, Garrod DR et al. Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. Journal of Investigative Dermatology. 1997;109(2):127-131.
Hashimoto, Takashi ; Kiyokawa, Chie ; Mori, Osamu ; Miyasato, Minoru ; Chidgey, Martyn A J ; Garrod, David R. ; Kobayashi, Yasushi ; Komori, Koji ; Ishii, Ken ; Amagai, Masayuki ; Nishikawa, Takeji. / Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus. In: Journal of Investigative Dermatology. 1997 ; Vol. 109, No. 2. pp. 127-131.
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abstract = "IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.",
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