Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane

H. Shimizu, T. Masunaga, A. Ishiko, K. Matsumura, T. Hashimoto, T. Nishikawa, N. Domloge-Hultsch, Z. Lazarova, K. B. Yancey

Research output: Contribution to journalArticle

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Abstract

Indirect immunogold electron microscopy studies of cryofixed, freeze-substituted, and post-embedded normal human skin were performed to localize precisely the ultrastructural binding site of circulating autoantibodies from two groups of patients with cicatricial pemphigoid. One group of patients had circulating IgG autoantibodies that bound the dermal side of 1 M NaCl-split skin and immunoprecipitated epiligrin. The other group of patients had circulating IgG autoantibodies directed against the epidermal side of 1 M NaCl-split skin and showed no specific reactivity to any keratinocyte polypeptide by immunoprecipitation. IgG autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid bound the lowermost aspect of the lamina lucida at its interface with the lamina densa; the greatest staining was seen beneath and beside hemidesmosomes. In contrast, IgG from cicatricial pemphigoid patients whose autoantibodies bound the epidermal side of 1 M NaCl-split skin localized to hemidesmosomes and the junction between hemidesmosomes and the plasma membranes of basal keratinocytes. Although the latter staining pattern is similar to that observed with anti-BPAG2 autoantibodies, sera from our patients with cicatricial pemphigoid did not bind BPAG2 in immunoprecipitation studies of radiolabeled human keratinocyte extracts or show immunoblot reactivity to a fusion protein corresponding to the immunodominant epitope of this polypeptide. These studies demonstrate the following: 1) Autoantibodies from patients with anti-epiligrin cicatricial pemphigoid consistently bind the lower lamina lucida at its interface with the lamina densa; and 2) other patients with the same phenotype may have IgG autoantibodies against yet-unknown epitopes in basal keratinocytes.

Original languageEnglish (US)
Pages (from-to)370-373
Number of pages4
JournalJournal of Investigative Dermatology
Volume104
Issue number3
StatePublished - 1995

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Benign Mucous Membrane Pemphigoid
Basement Membrane
Autoantibodies
Hemidesmosomes
Keratinocytes
Immunoglobulin G
Skin
Immunoprecipitation
Reactivity (nuclear)
Staining and Labeling
Immunodominant Epitopes
Peptides
Cell membranes
Electron microscopy
Epitopes
Electron Microscopy
Fusion reactions
Binding Sites
Cell Membrane
Phenotype

Keywords

  • autoimmunity
  • bullous diseases
  • epiligrin
  • ultrastructure

ASJC Scopus subject areas

  • Dermatology

Cite this

Shimizu, H., Masunaga, T., Ishiko, A., Matsumura, K., Hashimoto, T., Nishikawa, T., ... Yancey, K. B. (1995). Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane. Journal of Investigative Dermatology, 104(3), 370-373.

Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane. / Shimizu, H.; Masunaga, T.; Ishiko, A.; Matsumura, K.; Hashimoto, T.; Nishikawa, T.; Domloge-Hultsch, N.; Lazarova, Z.; Yancey, K. B.

In: Journal of Investigative Dermatology, Vol. 104, No. 3, 1995, p. 370-373.

Research output: Contribution to journalArticle

Shimizu, H, Masunaga, T, Ishiko, A, Matsumura, K, Hashimoto, T, Nishikawa, T, Domloge-Hultsch, N, Lazarova, Z & Yancey, KB 1995, 'Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane', Journal of Investigative Dermatology, vol. 104, no. 3, pp. 370-373.
Shimizu H, Masunaga T, Ishiko A, Matsumura K, Hashimoto T, Nishikawa T et al. Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane. Journal of Investigative Dermatology. 1995;104(3):370-373.
Shimizu, H. ; Masunaga, T. ; Ishiko, A. ; Matsumura, K. ; Hashimoto, T. ; Nishikawa, T. ; Domloge-Hultsch, N. ; Lazarova, Z. ; Yancey, K. B. / Autoantibodies from patients with cicatricial pemphigoid target different sites in epidermal basement membrane. In: Journal of Investigative Dermatology. 1995 ; Vol. 104, No. 3. pp. 370-373.
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abstract = "Indirect immunogold electron microscopy studies of cryofixed, freeze-substituted, and post-embedded normal human skin were performed to localize precisely the ultrastructural binding site of circulating autoantibodies from two groups of patients with cicatricial pemphigoid. One group of patients had circulating IgG autoantibodies that bound the dermal side of 1 M NaCl-split skin and immunoprecipitated epiligrin. The other group of patients had circulating IgG autoantibodies directed against the epidermal side of 1 M NaCl-split skin and showed no specific reactivity to any keratinocyte polypeptide by immunoprecipitation. IgG autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid bound the lowermost aspect of the lamina lucida at its interface with the lamina densa; the greatest staining was seen beneath and beside hemidesmosomes. In contrast, IgG from cicatricial pemphigoid patients whose autoantibodies bound the epidermal side of 1 M NaCl-split skin localized to hemidesmosomes and the junction between hemidesmosomes and the plasma membranes of basal keratinocytes. Although the latter staining pattern is similar to that observed with anti-BPAG2 autoantibodies, sera from our patients with cicatricial pemphigoid did not bind BPAG2 in immunoprecipitation studies of radiolabeled human keratinocyte extracts or show immunoblot reactivity to a fusion protein corresponding to the immunodominant epitope of this polypeptide. These studies demonstrate the following: 1) Autoantibodies from patients with anti-epiligrin cicatricial pemphigoid consistently bind the lower lamina lucida at its interface with the lamina densa; and 2) other patients with the same phenotype may have IgG autoantibodies against yet-unknown epitopes in basal keratinocytes.",
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AU - Matsumura, K.

AU - Hashimoto, T.

AU - Nishikawa, T.

AU - Domloge-Hultsch, N.

AU - Lazarova, Z.

AU - Yancey, K. B.

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