Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice

Background: Anti-neutrophil cytoplasmic antibody vasculitis is characterised by antibodies to myeloperoxidase or proteinase 3. Previous work in murine anti-myeloperoxidase vasculitis has shown a role for the alternative pathway complement component factor B and the anaphylotoxin C5a. However, mice d...

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Autores principales:	Fernanda Flórez-Barrós, Simon J. Freeley, El Li Tham, Michael G. Robson
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/017d11c000104d6e89c35a1cbfbd2021
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spelling	oai:doaj.org-article:017d11c000104d6e89c35a1cbfbd20212021-12-02T12:40:24ZExperimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice2673-363310.1159/000521233https://doaj.org/article/017d11c000104d6e89c35a1cbfbd20212021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/521233https://doaj.org/toc/2673-3633Background: Anti-neutrophil cytoplasmic antibody vasculitis is characterised by antibodies to myeloperoxidase or proteinase 3. Previous work in murine anti-myeloperoxidase vasculitis has shown a role for the alternative pathway complement component factor B and the anaphylotoxin C5a. However, mice deficient in properdin, which stabilizes the alternative pathway convertase, were not protected. VISTA-deficient mice were protected in the nephrotoxic nephritis model but the role of VISTA in anti-myeloperoxidase vasculitis is unknown. Objectives: This study had two aims. Firstly, we attempted to reproduce previous findings on the role of factor B in anti-myeloperoxidase vasculitis. Secondly, we examined the role of VISTA in this model, in order to see if the protection in the nephrotoxic nephritis model extended to anti-myeloperoxidase vasculitis. Methods: Anti-myeloperoxidase vasculitis was induced in wildtype, factor B, or VISTA deficient mice. Disease was assessed by quanitfying glomerular crescents and macrophages, in addition to albuminuria and serum creatinine. Results: When wild type and factor B deficient mice were compared, there were no differences in any of the histological or biochemical parameters of disease assessed. Similarly, when wild type or VISTA defiicent mice were compared, there were no differences. Conclusions: Factor B deficient mice were not protected which is in contrast to previous studies. Therefore alternative pathway activation is not essential in this model, under the conditions used in this study. VISTA deficient mice were not protected, suggesting that therapies targetting VISTA may not be effective in vasculitis.Fernanda Flórez-BarrósSimon J. FreeleyEl Li ThamMichael G. RobsonKarger PublishersarticleDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENGlomerular Diseases (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Diseases of the endocrine glands. Clinical endocrinology RC648-665 Fernanda Flórez-Barrós Simon J. Freeley El Li Tham Michael G. Robson Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice
description	Background: Anti-neutrophil cytoplasmic antibody vasculitis is characterised by antibodies to myeloperoxidase or proteinase 3. Previous work in murine anti-myeloperoxidase vasculitis has shown a role for the alternative pathway complement component factor B and the anaphylotoxin C5a. However, mice deficient in properdin, which stabilizes the alternative pathway convertase, were not protected. VISTA-deficient mice were protected in the nephrotoxic nephritis model but the role of VISTA in anti-myeloperoxidase vasculitis is unknown. Objectives: This study had two aims. Firstly, we attempted to reproduce previous findings on the role of factor B in anti-myeloperoxidase vasculitis. Secondly, we examined the role of VISTA in this model, in order to see if the protection in the nephrotoxic nephritis model extended to anti-myeloperoxidase vasculitis. Methods: Anti-myeloperoxidase vasculitis was induced in wildtype, factor B, or VISTA deficient mice. Disease was assessed by quanitfying glomerular crescents and macrophages, in addition to albuminuria and serum creatinine. Results: When wild type and factor B deficient mice were compared, there were no differences in any of the histological or biochemical parameters of disease assessed. Similarly, when wild type or VISTA defiicent mice were compared, there were no differences. Conclusions: Factor B deficient mice were not protected which is in contrast to previous studies. Therefore alternative pathway activation is not essential in this model, under the conditions used in this study. VISTA deficient mice were not protected, suggesting that therapies targetting VISTA may not be effective in vasculitis.
format	article
author	Fernanda Flórez-Barrós Simon J. Freeley El Li Tham Michael G. Robson
author_facet	Fernanda Flórez-Barrós Simon J. Freeley El Li Tham Michael G. Robson
author_sort	Fernanda Flórez-Barrós
title	Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice
title_short	Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice
title_full	Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice
title_fullStr	Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice
title_full_unstemmed	Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice
title_sort	experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor b or vista deficient mice
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/017d11c000104d6e89c35a1cbfbd2021
work_keys_str_mv	AT fernandaflorezbarros experimentallyinducedantimyeloperoxidasevasculitisisnotattenuatedinfactorborvistadeficientmice AT simonjfreeley experimentallyinducedantimyeloperoxidasevasculitisisnotattenuatedinfactorborvistadeficientmice AT ellitham experimentallyinducedantimyeloperoxidasevasculitisisnotattenuatedinfactorborvistadeficientmice AT michaelgrobson experimentallyinducedantimyeloperoxidasevasculitisisnotattenuatedinfactorborvistadeficientmice
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Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice

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