Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice

<h4>Background</h4> Pemphigus vulgaris (PV) is a rare autoimmune blistering disease characterized by the development of autoantibodies targeting desmoglein (Dsg) 3, but also against Dsg1 in mucocutaneous disease. Given that existing PV animal models only recapitulate aspects of the disea...

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Autores principales:	Katharina Boch, Sören Dräger, Detlef Zillikens, Christoph Hudemann, Christoph M. Hammers, Sabrina Patzelt, Enno Schmidt, Ewan A. Langan, Rüdiger Eming, Ralf J. Ludwig, Katja Bieber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c460bbe3c9964bc3b4f88249fe8bfd15
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spelling	oai:doaj.org-article:c460bbe3c9964bc3b4f88249fe8bfd152021-11-11T07:14:47ZImmunization with desmoglein 3 induces non-pathogenic autoantibodies in mice1932-6203https://doaj.org/article/c460bbe3c9964bc3b4f88249fe8bfd152021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565724/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4> Pemphigus vulgaris (PV) is a rare autoimmune blistering disease characterized by the development of autoantibodies targeting desmoglein (Dsg) 3, but also against Dsg1 in mucocutaneous disease. Given that existing PV animal models only recapitulate aspects of the disease, we aimed to establish a more comprehensive disease model based on the immunization of mice with PV autoantigen(s). <h4>Methods</h4> The following immunization strategies were tested: (i) C57Bl/6J, B6.SJL-H2s C3c/1CyJ, DBA2/J, or SJL/J mice were immunized with recombinant murine Dsg3 (mDsg3), (ii) DBA2/J and SJL/J mice were immunized with mDsg3 and additionally injected a single non-blister inducing dose of exfoliative toxin A (ETA), and (iii) DBA2/J and SJL/J mice were immunized with human Dsg (hDsg) 1 and 3. <h4>Results</h4> Despite the induction of autoantibodies in each immunization protocol, the mice did not develop a clinical phenotype. Tissue-bound autoantibodies were not detected in the skin or mucosa. Circulating autoantibodies did not bind to the native antigen in indirect immunofluorescence microscopy using monkey esophagus as a substrate. <h4>Conclusion</h4> Immunization with PV autoantigens induced non-pathogenic Dsg1/3 antibodies, but did not cause skin/mucous membrane disease in mice. These findings, confirmed by failure of binding of the induced autoantibodies to their target in the skin, suggest that the autoantibodies which were formed were unable to bind to the conformational epitope present in vivo.Katharina BochSören DrägerDetlef ZillikensChristoph HudemannChristoph M. HammersSabrina PatzeltEnno SchmidtEwan A. LanganRüdiger EmingRalf J. LudwigKatja BieberPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katharina Boch Sören Dräger Detlef Zillikens Christoph Hudemann Christoph M. Hammers Sabrina Patzelt Enno Schmidt Ewan A. Langan Rüdiger Eming Ralf J. Ludwig Katja Bieber Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
description	<h4>Background</h4> Pemphigus vulgaris (PV) is a rare autoimmune blistering disease characterized by the development of autoantibodies targeting desmoglein (Dsg) 3, but also against Dsg1 in mucocutaneous disease. Given that existing PV animal models only recapitulate aspects of the disease, we aimed to establish a more comprehensive disease model based on the immunization of mice with PV autoantigen(s). <h4>Methods</h4> The following immunization strategies were tested: (i) C57Bl/6J, B6.SJL-H2s C3c/1CyJ, DBA2/J, or SJL/J mice were immunized with recombinant murine Dsg3 (mDsg3), (ii) DBA2/J and SJL/J mice were immunized with mDsg3 and additionally injected a single non-blister inducing dose of exfoliative toxin A (ETA), and (iii) DBA2/J and SJL/J mice were immunized with human Dsg (hDsg) 1 and 3. <h4>Results</h4> Despite the induction of autoantibodies in each immunization protocol, the mice did not develop a clinical phenotype. Tissue-bound autoantibodies were not detected in the skin or mucosa. Circulating autoantibodies did not bind to the native antigen in indirect immunofluorescence microscopy using monkey esophagus as a substrate. <h4>Conclusion</h4> Immunization with PV autoantigens induced non-pathogenic Dsg1/3 antibodies, but did not cause skin/mucous membrane disease in mice. These findings, confirmed by failure of binding of the induced autoantibodies to their target in the skin, suggest that the autoantibodies which were formed were unable to bind to the conformational epitope present in vivo.
format	article
author	Katharina Boch Sören Dräger Detlef Zillikens Christoph Hudemann Christoph M. Hammers Sabrina Patzelt Enno Schmidt Ewan A. Langan Rüdiger Eming Ralf J. Ludwig Katja Bieber
author_facet	Katharina Boch Sören Dräger Detlef Zillikens Christoph Hudemann Christoph M. Hammers Sabrina Patzelt Enno Schmidt Ewan A. Langan Rüdiger Eming Ralf J. Ludwig Katja Bieber
author_sort	Katharina Boch
title	Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
title_short	Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
title_full	Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
title_fullStr	Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
title_full_unstemmed	Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
title_sort	immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c460bbe3c9964bc3b4f88249fe8bfd15
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Immunization with desmoglein 3 induces non-pathogenic autoantibodies in mice

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