Preclinical detection of variant CJD and BSE prions in blood.

The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE) agent. More recently, secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy dono...

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Autores principales:	Caroline Lacroux, Emmanuel Comoy, Mohammed Moudjou, Armand Perret-Liaudet, Séverine Lugan, Claire Litaise, Hugh Simmons, Christelle Jas-Duval, Isabelle Lantier, Vincent Béringue, Martin Groschup, Guillaume Fichet, Pierrette Costes, Nathalie Streichenberger, Frederic Lantier, Jean Philippe Deslys, Didier Vilette, Olivier Andréoletti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a37cfeacd0334014b4ea266934ffded8
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spelling	oai:doaj.org-article:a37cfeacd0334014b4ea266934ffded82021-11-11T06:06:10ZPreclinical detection of variant CJD and BSE prions in blood.1553-73661553-737410.1371/journal.ppat.1004202https://doaj.org/article/a37cfeacd0334014b4ea266934ffded82014-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24945656/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE) agent. More recently, secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors who later went on to develop the disease. As there is no validated assay for detection of vCJD/BSE infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific in vitro amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q171 PrP substrates provided the best amplification performances. These results indicate that the homology of PrP amino-acid sequence between the seed and the substrate is not the crucial determinant of the vCJD agent propagation in vitro. The ability of this method to detect endogenous vCJD/BSE agent in the blood was then defined. In both sheep and primate models of the disease, the assay enabled the identification of infected individuals in the early preclinical stage of the incubation period. Finally, sample panels that included buffy coat from vCJD affected patients and healthy controls were tested blind. The assay identified three out of the four tested vCJD affected patients and no false positive was observed in 141 healthy controls. The negative results observed in one of the tested vCJD cases concurs with results reported by others using a different vCJD agent blood detection assay and raises the question of the potential absence of prionemia in certain patients.Caroline LacrouxEmmanuel ComoyMohammed MoudjouArmand Perret-LiaudetSéverine LuganClaire LitaiseHugh SimmonsChristelle Jas-DuvalIsabelle LantierVincent BéringueMartin GroschupGuillaume FichetPierrette CostesNathalie StreichenbergerFrederic LantierJean Philippe DeslysDidier ViletteOlivier AndréolettiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 6, p e1004202 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Caroline Lacroux Emmanuel Comoy Mohammed Moudjou Armand Perret-Liaudet Séverine Lugan Claire Litaise Hugh Simmons Christelle Jas-Duval Isabelle Lantier Vincent Béringue Martin Groschup Guillaume Fichet Pierrette Costes Nathalie Streichenberger Frederic Lantier Jean Philippe Deslys Didier Vilette Olivier Andréoletti Preclinical detection of variant CJD and BSE prions in blood.
description	The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE) agent. More recently, secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors who later went on to develop the disease. As there is no validated assay for detection of vCJD/BSE infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific in vitro amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q171 PrP substrates provided the best amplification performances. These results indicate that the homology of PrP amino-acid sequence between the seed and the substrate is not the crucial determinant of the vCJD agent propagation in vitro. The ability of this method to detect endogenous vCJD/BSE agent in the blood was then defined. In both sheep and primate models of the disease, the assay enabled the identification of infected individuals in the early preclinical stage of the incubation period. Finally, sample panels that included buffy coat from vCJD affected patients and healthy controls were tested blind. The assay identified three out of the four tested vCJD affected patients and no false positive was observed in 141 healthy controls. The negative results observed in one of the tested vCJD cases concurs with results reported by others using a different vCJD agent blood detection assay and raises the question of the potential absence of prionemia in certain patients.
format	article
author	Caroline Lacroux Emmanuel Comoy Mohammed Moudjou Armand Perret-Liaudet Séverine Lugan Claire Litaise Hugh Simmons Christelle Jas-Duval Isabelle Lantier Vincent Béringue Martin Groschup Guillaume Fichet Pierrette Costes Nathalie Streichenberger Frederic Lantier Jean Philippe Deslys Didier Vilette Olivier Andréoletti
author_facet	Caroline Lacroux Emmanuel Comoy Mohammed Moudjou Armand Perret-Liaudet Séverine Lugan Claire Litaise Hugh Simmons Christelle Jas-Duval Isabelle Lantier Vincent Béringue Martin Groschup Guillaume Fichet Pierrette Costes Nathalie Streichenberger Frederic Lantier Jean Philippe Deslys Didier Vilette Olivier Andréoletti
author_sort	Caroline Lacroux
title	Preclinical detection of variant CJD and BSE prions in blood.
title_short	Preclinical detection of variant CJD and BSE prions in blood.
title_full	Preclinical detection of variant CJD and BSE prions in blood.
title_fullStr	Preclinical detection of variant CJD and BSE prions in blood.
title_full_unstemmed	Preclinical detection of variant CJD and BSE prions in blood.
title_sort	preclinical detection of variant cjd and bse prions in blood.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a37cfeacd0334014b4ea266934ffded8
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Preclinical detection of variant CJD and BSE prions in blood.

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