Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.

<h4>Introduction</h4>Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agals...

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Autores principales:	Saskia M Rombach, Johannes M F G Aerts, Ben J H M Poorthuis, Johanna E M Groener, Wilma Donker-Koopman, Erik Hendriks, Mina Mirzaian, Sijmen Kuiper, Frits A Wijburg, Carla E M Hollak, Gabor E Linthorst
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/430552f7237642d1bf77438f9ca510a1
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spelling	oai:doaj.org-article:430552f7237642d1bf77438f9ca510a12021-11-18T08:11:28ZLong-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.1932-620310.1371/journal.pone.0047805https://doaj.org/article/430552f7237642d1bf77438f9ca510a12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23094092/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agalsidase AB on Gb3 and lysoGb3 and clinical outcome in Fabry patients on ERT.<h4>Methods</h4>Adult male and female patients on ERT for at least one year were included. Urinary Gb3 was measured by HPLC, plasma lysoGb3 by LC-ESI-MS/MS and AB with a neutralization assay.<h4>Results</h4>Of the 59 patients evaluable patients, 0/30 females and 17/29 males developed anti-agalsidase antibodies (AB+). Only 3/17 males had transient (low) titers (tolerized). All AB+ patients developed antibodies during the first year of treatment. Change of agalsidase preparation (or dose) did not induce antibody formation. AB+ males had significant less decline in plasma lysoGb3 compared to AB- males (p = 0.04). Urinary Gb3 levels decreased markedly in AB- but remained comparable to baseline in AB+ males (p<0.01). (Lyso)Gb3 reduction in plasma and urine on ERT was correlated with LVmass reduction in females and development white matter lesions and stroke.<h4>Conclusion</h4>In male patients antibodies against aGal A remained present up to 10 years of ERT. The presence of these antibodies is associated with a less robust decrease in plasma lysoGb3 and a profound negative effect on urinary Gb3 reduction, which may reflect worse treatment outcome.Saskia M RombachJohannes M F G AertsBen J H M PoorthuisJohanna E M GroenerWilma Donker-KoopmanErik HendriksMina MirzaianSijmen KuiperFrits A WijburgCarla E M HollakGabor E LinthorstPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47805 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saskia M Rombach Johannes M F G Aerts Ben J H M Poorthuis Johanna E M Groener Wilma Donker-Koopman Erik Hendriks Mina Mirzaian Sijmen Kuiper Frits A Wijburg Carla E M Hollak Gabor E Linthorst Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
description	<h4>Introduction</h4>Enzyme replacement therapy (ERT) with alpha-Galactosidase A (aGal A) may cause antibody (AB) formation against aGal A in males with Fabry disease (FD). Anti agalsidase ABs negatively influence globotriaosylceramide (Gb3) reduction. We investigated the impact of agalsidase AB on Gb3 and lysoGb3 and clinical outcome in Fabry patients on ERT.<h4>Methods</h4>Adult male and female patients on ERT for at least one year were included. Urinary Gb3 was measured by HPLC, plasma lysoGb3 by LC-ESI-MS/MS and AB with a neutralization assay.<h4>Results</h4>Of the 59 patients evaluable patients, 0/30 females and 17/29 males developed anti-agalsidase antibodies (AB+). Only 3/17 males had transient (low) titers (tolerized). All AB+ patients developed antibodies during the first year of treatment. Change of agalsidase preparation (or dose) did not induce antibody formation. AB+ males had significant less decline in plasma lysoGb3 compared to AB- males (p = 0.04). Urinary Gb3 levels decreased markedly in AB- but remained comparable to baseline in AB+ males (p<0.01). (Lyso)Gb3 reduction in plasma and urine on ERT was correlated with LVmass reduction in females and development white matter lesions and stroke.<h4>Conclusion</h4>In male patients antibodies against aGal A remained present up to 10 years of ERT. The presence of these antibodies is associated with a less robust decrease in plasma lysoGb3 and a profound negative effect on urinary Gb3 reduction, which may reflect worse treatment outcome.
format	article
author	Saskia M Rombach Johannes M F G Aerts Ben J H M Poorthuis Johanna E M Groener Wilma Donker-Koopman Erik Hendriks Mina Mirzaian Sijmen Kuiper Frits A Wijburg Carla E M Hollak Gabor E Linthorst
author_facet	Saskia M Rombach Johannes M F G Aerts Ben J H M Poorthuis Johanna E M Groener Wilma Donker-Koopman Erik Hendriks Mina Mirzaian Sijmen Kuiper Frits A Wijburg Carla E M Hollak Gabor E Linthorst
author_sort	Saskia M Rombach
title	Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
title_short	Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
title_full	Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
title_fullStr	Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
title_full_unstemmed	Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.
title_sort	long-term effect of antibodies against infused alpha-galactosidase a in fabry disease on plasma and urinary (lyso)gb3 reduction and treatment outcome.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/430552f7237642d1bf77438f9ca510a1
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Long-term effect of antibodies against infused alpha-galactosidase A in Fabry disease on plasma and urinary (lyso)Gb3 reduction and treatment outcome.

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