Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus foliaceus across different activity stages

K. Kamiya, Y. Aoyama, Osamu Yamasaki, A. Kamata, J. Yamagami, K. Iwatsuki, Y. Tokura

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)-treated Dsg3 enzyme-linked immunosorbent assay (ELISA) we have shown that the proportion of anti-Dsg3 antibodies against calcium-dependent epitopes decreased upon shifting to the inactive phase in patients with PV. Objectives: To analyse the epitope profiles of anti-Dsg1 antibodies across the different activity stages of PF. Methods: We evaluated five patients with PF who retained high serum levels of anti-Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA-treated and exfoliative toxin-treated ELISAs. To map the epitopes of anti-Dsg1 antibodies, immunoprecipitation-immunoblotting was performed using a set of Dsg1/Dsg2 domain-swapped molecules. Results: Anti-Dsg1 antibodies against the calcium-dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti-Dsg1 antibodies against the calcium-dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation-immunoblotting showed that most of the anti-Dsg1 antibodies bound to the extracellular domains (EC)1-2 of Dsg1. Conclusions: In patients with PF, the calcium-dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope.

Original languageEnglish
JournalBritish Journal of Dermatology
DOIs
Publication statusAccepted/In press - 2015

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Pemphigus
Autoantibodies
Epitopes
Anti-Idiotypic Antibodies
Calcium
Immunoprecipitation
Immunoblotting
Edetic Acid
Exfoliatins
Desmoglein 1
Enzyme-Linked Immunosorbent Assay
Antibodies
Serum
Autoimmune Diseases

ASJC Scopus subject areas

  • Dermatology

Cite this

Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus foliaceus across different activity stages. / Kamiya, K.; Aoyama, Y.; Yamasaki, Osamu; Kamata, A.; Yamagami, J.; Iwatsuki, K.; Tokura, Y.

In: British Journal of Dermatology, 2015.

Research output: Contribution to journalArticle

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abstract = "Background: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)-treated Dsg3 enzyme-linked immunosorbent assay (ELISA) we have shown that the proportion of anti-Dsg3 antibodies against calcium-dependent epitopes decreased upon shifting to the inactive phase in patients with PV. Objectives: To analyse the epitope profiles of anti-Dsg1 antibodies across the different activity stages of PF. Methods: We evaluated five patients with PF who retained high serum levels of anti-Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA-treated and exfoliative toxin-treated ELISAs. To map the epitopes of anti-Dsg1 antibodies, immunoprecipitation-immunoblotting was performed using a set of Dsg1/Dsg2 domain-swapped molecules. Results: Anti-Dsg1 antibodies against the calcium-dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti-Dsg1 antibodies against the calcium-dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation-immunoblotting showed that most of the anti-Dsg1 antibodies bound to the extracellular domains (EC)1-2 of Dsg1. Conclusions: In patients with PF, the calcium-dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope.",
author = "K. Kamiya and Y. Aoyama and Osamu Yamasaki and A. Kamata and J. Yamagami and K. Iwatsuki and Y. Tokura",
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T1 - Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus foliaceus across different activity stages

AU - Kamiya, K.

AU - Aoyama, Y.

AU - Yamasaki, Osamu

AU - Kamata, A.

AU - Yamagami, J.

AU - Iwatsuki, K.

AU - Tokura, Y.

PY - 2015

Y1 - 2015

N2 - Background: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)-treated Dsg3 enzyme-linked immunosorbent assay (ELISA) we have shown that the proportion of anti-Dsg3 antibodies against calcium-dependent epitopes decreased upon shifting to the inactive phase in patients with PV. Objectives: To analyse the epitope profiles of anti-Dsg1 antibodies across the different activity stages of PF. Methods: We evaluated five patients with PF who retained high serum levels of anti-Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA-treated and exfoliative toxin-treated ELISAs. To map the epitopes of anti-Dsg1 antibodies, immunoprecipitation-immunoblotting was performed using a set of Dsg1/Dsg2 domain-swapped molecules. Results: Anti-Dsg1 antibodies against the calcium-dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti-Dsg1 antibodies against the calcium-dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation-immunoblotting showed that most of the anti-Dsg1 antibodies bound to the extracellular domains (EC)1-2 of Dsg1. Conclusions: In patients with PF, the calcium-dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope.

AB - Background: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)-treated Dsg3 enzyme-linked immunosorbent assay (ELISA) we have shown that the proportion of anti-Dsg3 antibodies against calcium-dependent epitopes decreased upon shifting to the inactive phase in patients with PV. Objectives: To analyse the epitope profiles of anti-Dsg1 antibodies across the different activity stages of PF. Methods: We evaluated five patients with PF who retained high serum levels of anti-Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA-treated and exfoliative toxin-treated ELISAs. To map the epitopes of anti-Dsg1 antibodies, immunoprecipitation-immunoblotting was performed using a set of Dsg1/Dsg2 domain-swapped molecules. Results: Anti-Dsg1 antibodies against the calcium-dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti-Dsg1 antibodies against the calcium-dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation-immunoblotting showed that most of the anti-Dsg1 antibodies bound to the extracellular domains (EC)1-2 of Dsg1. Conclusions: In patients with PF, the calcium-dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope.

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DO - 10.1111/bjd.14098

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JO - British Journal of Dermatology

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