Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid

Abstract Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activat...

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Autores principales:	Pei Qiao, Erle Dang, Tianyu Cao, Hui Fang, Jieyu Zhang, Hongjiang Qiao, Gang Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f799adc11c2a48b79954883d0b0549c2
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spelling	oai:doaj.org-article:f799adc11c2a48b79954883d0b0549c22021-12-02T15:05:20ZDysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid10.1038/s41598-017-00235-32045-2322https://doaj.org/article/f799adc11c2a48b79954883d0b0549c22017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00235-3https://doaj.org/toc/2045-2322Abstract Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A antibody and C3a. Otherwise, the level of mCD46 was decreased in lesions of BP patients, whereas the complement activation was enhanced. We also found that CD46 knockdown in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Importantly, exogenous CD46 blocked complement activation in both healthy skin sections and keratinocytes induced by exposure to pathogenic antibodies from BP patients. These data suggest that CD46 deficiency is an important factor in BP pathogenesis and that increasing CD46 levels might be an effective treatment for BP.Pei QiaoErle DangTianyu CaoHui FangJieyu ZhangHongjiang QiaoGang WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pei Qiao Erle Dang Tianyu Cao Hui Fang Jieyu Zhang Hongjiang Qiao Gang Wang Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid
description	Abstract Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A antibody and C3a. Otherwise, the level of mCD46 was decreased in lesions of BP patients, whereas the complement activation was enhanced. We also found that CD46 knockdown in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Importantly, exogenous CD46 blocked complement activation in both healthy skin sections and keratinocytes induced by exposure to pathogenic antibodies from BP patients. These data suggest that CD46 deficiency is an important factor in BP pathogenesis and that increasing CD46 levels might be an effective treatment for BP.
format	article
author	Pei Qiao Erle Dang Tianyu Cao Hui Fang Jieyu Zhang Hongjiang Qiao Gang Wang
author_facet	Pei Qiao Erle Dang Tianyu Cao Hui Fang Jieyu Zhang Hongjiang Qiao Gang Wang
author_sort	Pei Qiao
title	Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid
title_short	Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid
title_full	Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid
title_fullStr	Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid
title_full_unstemmed	Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid
title_sort	dysregulation of mcd46 and scd46 contribute to the pathogenesis of bullous pemphigoid
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f799adc11c2a48b79954883d0b0549c2
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Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid

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