Pathogenicity of autoantibodies in anti-p200 pemphigoid.

Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoanti...

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Autores principales:	Katerina Vafia, Stephanie Groth, Tina Beckmann, Misa Hirose, Jenny Dworschak, Andreas Recke, Ralf J Ludwig, Takashi Hashimoto, Detlef Zillikens, Enno Schmidt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43a9fd71d5514725b2cbad679e1bc0e4
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spelling	oai:doaj.org-article:43a9fd71d5514725b2cbad679e1bc0e42021-11-18T07:11:16ZPathogenicity of autoantibodies in anti-p200 pemphigoid.1932-620310.1371/journal.pone.0041769https://doaj.org/article/43a9fd71d5514725b2cbad679e1bc0e42012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911854/?tool=EBIhttps://doaj.org/toc/1932-6203Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES) using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7) induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609). Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ) by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid.Katerina VafiaStephanie GrothTina BeckmannMisa HiroseJenny DworschakAndreas ReckeRalf J LudwigTakashi HashimotoDetlef ZillikensEnno SchmidtPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41769 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katerina Vafia Stephanie Groth Tina Beckmann Misa Hirose Jenny Dworschak Andreas Recke Ralf J Ludwig Takashi Hashimoto Detlef Zillikens Enno Schmidt Pathogenicity of autoantibodies in anti-p200 pemphigoid.
description	Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES) using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7) induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609). Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ) by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid.
format	article
author	Katerina Vafia Stephanie Groth Tina Beckmann Misa Hirose Jenny Dworschak Andreas Recke Ralf J Ludwig Takashi Hashimoto Detlef Zillikens Enno Schmidt
author_facet	Katerina Vafia Stephanie Groth Tina Beckmann Misa Hirose Jenny Dworschak Andreas Recke Ralf J Ludwig Takashi Hashimoto Detlef Zillikens Enno Schmidt
author_sort	Katerina Vafia
title	Pathogenicity of autoantibodies in anti-p200 pemphigoid.
title_short	Pathogenicity of autoantibodies in anti-p200 pemphigoid.
title_full	Pathogenicity of autoantibodies in anti-p200 pemphigoid.
title_fullStr	Pathogenicity of autoantibodies in anti-p200 pemphigoid.
title_full_unstemmed	Pathogenicity of autoantibodies in anti-p200 pemphigoid.
title_sort	pathogenicity of autoantibodies in anti-p200 pemphigoid.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/43a9fd71d5514725b2cbad679e1bc0e4
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Pathogenicity of autoantibodies in anti-p200 pemphigoid.

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