Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.

<h4>Background</h4>Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed u...

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Autores principales:	Alain Van Dorsselaer, Christine Carapito, François Delalande, Christine Schaeffer-Reiss, Daniele Thierse, Hélène Diemer, Douglas S McNair, Daniel Krewski, Neil R Cashman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83a4cd61cec54304a0d6f27faf682c40
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spelling	oai:doaj.org-article:83a4cd61cec54304a0d6f27faf682c402021-11-18T06:56:56ZDetection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.1932-620310.1371/journal.pone.0017815https://doaj.org/article/83a4cd61cec54304a0d6f27faf682c402011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21448279/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).<h4>Methodology/principal findings</h4>Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products.<h4>Conclusions/significance</h4>The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products.Alain Van DorsselaerChristine CarapitoFrançois DelalandeChristine Schaeffer-ReissDaniele ThierseHélène DiemerDouglas S McNairDaniel KrewskiNeil R CashmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17815 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alain Van Dorsselaer Christine Carapito François Delalande Christine Schaeffer-Reiss Daniele Thierse Hélène Diemer Douglas S McNair Daniel Krewski Neil R Cashman Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
description	<h4>Background</h4>Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).<h4>Methodology/principal findings</h4>Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products.<h4>Conclusions/significance</h4>The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products.
format	article
author	Alain Van Dorsselaer Christine Carapito François Delalande Christine Schaeffer-Reiss Daniele Thierse Hélène Diemer Douglas S McNair Daniel Krewski Neil R Cashman
author_facet	Alain Van Dorsselaer Christine Carapito François Delalande Christine Schaeffer-Reiss Daniele Thierse Hélène Diemer Douglas S McNair Daniel Krewski Neil R Cashman
author_sort	Alain Van Dorsselaer
title	Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
title_short	Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
title_full	Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
title_fullStr	Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
title_full_unstemmed	Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
title_sort	detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/83a4cd61cec54304a0d6f27faf682c40
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Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.

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