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Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita

Collagen VII is the main constituent of the anchoring fibrils, important adhesive structures that attach the epidermis to the dermal extracellular matrix. Two disorders are caused by dysfunction of collagen VII, both characterized by skin and mucosa fragility, epidermolysis bullosa acquisita (EBA) a...

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Autores principales: Schauer, Franziska, Nyström, Alexander, Kunz, Manfred, Hübner, Stefanie, Scholl, Sarah, Athanasiou, Ioannis, Alter, Svenja, Fischer, Judith, Has, Cristina, Kiritsi, Dimitra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021387/
https://www.ncbi.nlm.nih.gov/pubmed/35464429
http://dx.doi.org/10.3389/fimmu.2022.883967
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author Schauer, Franziska
Nyström, Alexander
Kunz, Manfred
Hübner, Stefanie
Scholl, Sarah
Athanasiou, Ioannis
Alter, Svenja
Fischer, Judith
Has, Cristina
Kiritsi, Dimitra
author_facet Schauer, Franziska
Nyström, Alexander
Kunz, Manfred
Hübner, Stefanie
Scholl, Sarah
Athanasiou, Ioannis
Alter, Svenja
Fischer, Judith
Has, Cristina
Kiritsi, Dimitra
author_sort Schauer, Franziska
collection PubMed
description Collagen VII is the main constituent of the anchoring fibrils, important adhesive structures that attach the epidermis to the dermal extracellular matrix. Two disorders are caused by dysfunction of collagen VII, both characterized by skin and mucosa fragility, epidermolysis bullosa acquisita (EBA) and dystrophic epidermolysis bullosa (DEB). EBA and DEB share high clinical similarities with significant difference in patients’ age of onset and pathogenesis. Our patients presented with severe and recalcitrant mechanobullous EBA with characteristic DIF, IIF and ELISA diagnostics. But in both women recessive COL7A1 variants were also found, in a monoallelic state. Collagen VII from EBA keratinocytes of our cases was significantly more vulnerable to proteolytic degradation than control keratinocytes, hinting that the heterozygous pathogenic variants were sufficient to destabilize the molecule in vitro. Thus, even if the amount and functionality of mutant and normal type VII collagen polypeptides is sufficient to assure dermal-epidermal adhesion in healthy individuals, the functionally-impaired proteins are probably more prone to development of autoantibodies against them. Our work suggests that testing for COL7A1 genetic variants should be considered in patients with EBA, which either have a patient history hinting towards underlying dystrophic epidermolysis bullosa or pose therapeutic challenges.
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spelling pubmed-90213872022-04-22 Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita Schauer, Franziska Nyström, Alexander Kunz, Manfred Hübner, Stefanie Scholl, Sarah Athanasiou, Ioannis Alter, Svenja Fischer, Judith Has, Cristina Kiritsi, Dimitra Front Immunol Immunology Collagen VII is the main constituent of the anchoring fibrils, important adhesive structures that attach the epidermis to the dermal extracellular matrix. Two disorders are caused by dysfunction of collagen VII, both characterized by skin and mucosa fragility, epidermolysis bullosa acquisita (EBA) and dystrophic epidermolysis bullosa (DEB). EBA and DEB share high clinical similarities with significant difference in patients’ age of onset and pathogenesis. Our patients presented with severe and recalcitrant mechanobullous EBA with characteristic DIF, IIF and ELISA diagnostics. But in both women recessive COL7A1 variants were also found, in a monoallelic state. Collagen VII from EBA keratinocytes of our cases was significantly more vulnerable to proteolytic degradation than control keratinocytes, hinting that the heterozygous pathogenic variants were sufficient to destabilize the molecule in vitro. Thus, even if the amount and functionality of mutant and normal type VII collagen polypeptides is sufficient to assure dermal-epidermal adhesion in healthy individuals, the functionally-impaired proteins are probably more prone to development of autoantibodies against them. Our work suggests that testing for COL7A1 genetic variants should be considered in patients with EBA, which either have a patient history hinting towards underlying dystrophic epidermolysis bullosa or pose therapeutic challenges. Frontiers Media S.A. 2022-04-07 /pmc/articles/PMC9021387/ /pubmed/35464429 http://dx.doi.org/10.3389/fimmu.2022.883967 Text en Copyright © 2022 Schauer, Nyström, Kunz, Hübner, Scholl, Athanasiou, Alter, Fischer, Has and Kiritsi 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
Schauer, Franziska
Nyström, Alexander
Kunz, Manfred
Hübner, Stefanie
Scholl, Sarah
Athanasiou, Ioannis
Alter, Svenja
Fischer, Judith
Has, Cristina
Kiritsi, Dimitra
Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita
title Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita
title_full Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita
title_fullStr Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita
title_full_unstemmed Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita
title_short Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita
title_sort case report: diagnostic and therapeutic challenges in severe mechanobullous epidermolysis bullosa acquisita
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021387/
https://www.ncbi.nlm.nih.gov/pubmed/35464429
http://dx.doi.org/10.3389/fimmu.2022.883967
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