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Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo

Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal m...

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Autores principales: Wang, Xue, Wang, Rui, Bu, Dingfang, Wang, Leyi, Zhang, Yuexin, Chang, Yuan, Zhang, Chenyang, Chen, Xixue, Zhu, Xuejun, Liu, Zhi, Wang, Mingyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332891/
https://www.ncbi.nlm.nih.gov/pubmed/35911677
http://dx.doi.org/10.3389/fimmu.2022.886226
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author Wang, Xue
Wang, Rui
Bu, Dingfang
Wang, Leyi
Zhang, Yuexin
Chang, Yuan
Zhang, Chenyang
Chen, Xixue
Zhu, Xuejun
Liu, Zhi
Wang, Mingyue
author_facet Wang, Xue
Wang, Rui
Bu, Dingfang
Wang, Leyi
Zhang, Yuexin
Chang, Yuan
Zhang, Chenyang
Chen, Xixue
Zhu, Xuejun
Liu, Zhi
Wang, Mingyue
author_sort Wang, Xue
collection PubMed
description Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. In vitro dispase-dependent keratinocyte dissociation assay and in vivo IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP.
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spelling pubmed-93328912022-07-29 Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo Wang, Xue Wang, Rui Bu, Dingfang Wang, Leyi Zhang, Yuexin Chang, Yuan Zhang, Chenyang Chen, Xixue Zhu, Xuejun Liu, Zhi Wang, Mingyue Front Immunol Immunology Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. In vitro dispase-dependent keratinocyte dissociation assay and in vivo IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9332891/ /pubmed/35911677 http://dx.doi.org/10.3389/fimmu.2022.886226 Text en Copyright © 2022 Wang, Wang, Bu, Wang, Zhang, Chang, Zhang, Chen, Zhu, Liu and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Xue
Wang, Rui
Bu, Dingfang
Wang, Leyi
Zhang, Yuexin
Chang, Yuan
Zhang, Chenyang
Chen, Xixue
Zhu, Xuejun
Liu, Zhi
Wang, Mingyue
Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
title Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
title_full Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
title_fullStr Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
title_full_unstemmed Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
title_short Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo
title_sort paraneoplastic pemphigus autoantibodies against c-terminus of desmoplakin induced acantholysis in vitro and in vivo
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332891/
https://www.ncbi.nlm.nih.gov/pubmed/35911677
http://dx.doi.org/10.3389/fimmu.2022.886226
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