Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity

[EN] Bovine paratuberculosis (PTB) is a chronic granulomatous enteritis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), responsible for important economic losses in the dairy industry. Current diagnostic methods have low sensitivities for detection of latent forms of MAP infection, def...

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Autores: Blanco Vázquez, Cristina, Alonso Hearn, Marta, Juste, Ramón A., Canive, María, Iglesias, Tania, Iglesias, Natalia, Amado, Javier, Vicente, Fernando, Balseiro Morales, Ana María, Casais, Rosa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/19081
Acceso en línea:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236336
https://hdl.handle.net/10612/19081
Access Level:acceso abierto
Palabra clave:Sanidad animal
Diagnostic
Mycobacterium avium subsp. paratuberculosis
3109 Ciencias Veterinarias
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oai_identifier_str oai:buleria.unileon.es:10612/19081
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
title Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
spellingShingle Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
Blanco Vázquez, Cristina
Sanidad animal
Diagnostic
Mycobacterium avium subsp. paratuberculosis
3109 Ciencias Veterinarias
title_short Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
title_full Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
title_fullStr Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
title_full_unstemmed Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
title_sort Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity
dc.creator.none.fl_str_mv Blanco Vázquez, Cristina
Alonso Hearn, Marta
Juste, Ramón A.
Canive, María
Iglesias, Tania
Iglesias, Natalia
Amado, Javier
Vicente, Fernando
Balseiro Morales, Ana María
Casais, Rosa
author Blanco Vázquez, Cristina
author_facet Blanco Vázquez, Cristina
Alonso Hearn, Marta
Juste, Ramón A.
Canive, María
Iglesias, Tania
Iglesias, Natalia
Amado, Javier
Vicente, Fernando
Balseiro Morales, Ana María
Casais, Rosa
author_role author
author2 Alonso Hearn, Marta
Juste, Ramón A.
Canive, María
Iglesias, Tania
Iglesias, Natalia
Amado, Javier
Vicente, Fernando
Balseiro Morales, Ana María
Casais, Rosa
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sanidad Animal
Facultad de Veterinaria
dc.subject.none.fl_str_mv Sanidad animal
Diagnostic
Mycobacterium avium subsp. paratuberculosis
3109 Ciencias Veterinarias
topic Sanidad animal
Diagnostic
Mycobacterium avium subsp. paratuberculosis
3109 Ciencias Veterinarias
description [EN] Bovine paratuberculosis (PTB) is a chronic granulomatous enteritis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), responsible for important economic losses in the dairy industry. Current diagnostic methods have low sensitivities for detection of latent forms of MAP infection, defined by focal granulomatous lesions and scarce humoral response or MAP presence. In contrast, patent infections correspond to multifocal and diffuse types of enteritis where there is increased antibody production, and substantial mycobacterial load. Our previous RNA-Seq analysis allowed the selection of five candidate biomarkers overexpressed in peripheral blood of MAP infected Holstein cows with focal (ABCA13 and MMP8) and diffuse (FAM84A, SPARC and DES) lesions vs. control animals with no detectable PTB-associated lesions in intestine and regional lymph nodes. The aim of the current study was to assess the PTB diagnostic potential of commercial ELISAs designed for the specific detection of these biomarkers. The ability of these ELISAs to identify animals with latent and/or patent forms of MAP infection was investigated using serum from naturally infected cattle (n = 88) and non-infected control animals (n = 67). ROC analysis revealed that the ABCA13-based ELISA showed the highest diagnostic accuracy for the detection of infected animals with focal lesions (AUC 0.837, sensitivity 79.25% and specificity 88.06%) and with any type of histological lesion (AUC 0.793, sensitivity 69.41% and specificity 86.57%) improving on the diagnostic performance of the popular IDEXX ELISA and other conventional diagnostic methods. SPARC and MMP8 showed the highest diagnostic accuracy for the detection of animals with multifocal (AUC 0.852) and diffuse lesions (AUC 0.831), respectively. In conclusion, our results suggest that quantification of ABCA13, SPARC and MMP8 by ELISA has the potential for implementation as a diagnostic tool to reliably identify MAP infection, greatly improving early detection of MAP latent infections when antibody responses and fecal shedding are undetectable using conventional diagnostic methods
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236336
https://hdl.handle.net/10612/19081
url https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236336
https://hdl.handle.net/10612/19081
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/RTA2014-00009-C02-02
info:eu-repo/grantAgreement/AEI/ Programa Estatal de I+D+i Orientada a los Retos de la Sociedad / RTI2018-094192-R-C22,
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Universidad de León
instname_str Universidad de León
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivityBlanco Vázquez, CristinaAlonso Hearn, MartaJuste, Ramón A.Canive, MaríaIglesias, TaniaIglesias, NataliaAmado, JavierVicente, FernandoBalseiro Morales, Ana MaríaCasais, RosaSanidad animalDiagnosticMycobacterium avium subsp. paratuberculosis3109 Ciencias Veterinarias[EN] Bovine paratuberculosis (PTB) is a chronic granulomatous enteritis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), responsible for important economic losses in the dairy industry. Current diagnostic methods have low sensitivities for detection of latent forms of MAP infection, defined by focal granulomatous lesions and scarce humoral response or MAP presence. In contrast, patent infections correspond to multifocal and diffuse types of enteritis where there is increased antibody production, and substantial mycobacterial load. Our previous RNA-Seq analysis allowed the selection of five candidate biomarkers overexpressed in peripheral blood of MAP infected Holstein cows with focal (ABCA13 and MMP8) and diffuse (FAM84A, SPARC and DES) lesions vs. control animals with no detectable PTB-associated lesions in intestine and regional lymph nodes. The aim of the current study was to assess the PTB diagnostic potential of commercial ELISAs designed for the specific detection of these biomarkers. The ability of these ELISAs to identify animals with latent and/or patent forms of MAP infection was investigated using serum from naturally infected cattle (n = 88) and non-infected control animals (n = 67). ROC analysis revealed that the ABCA13-based ELISA showed the highest diagnostic accuracy for the detection of infected animals with focal lesions (AUC 0.837, sensitivity 79.25% and specificity 88.06%) and with any type of histological lesion (AUC 0.793, sensitivity 69.41% and specificity 86.57%) improving on the diagnostic performance of the popular IDEXX ELISA and other conventional diagnostic methods. SPARC and MMP8 showed the highest diagnostic accuracy for the detection of animals with multifocal (AUC 0.852) and diffuse lesions (AUC 0.831), respectively. In conclusion, our results suggest that quantification of ABCA13, SPARC and MMP8 by ELISA has the potential for implementation as a diagnostic tool to reliably identify MAP infection, greatly improving early detection of MAP latent infections when antibody responses and fecal shedding are undetectable using conventional diagnostic methodsSIThis study was funded by 1) The National Institute for Agricultural Research (INIA, www.inia. es/inia/), project code: RTA-2014-00009-C02-02, R.C received this award, 2) The Spanish Ministry of Science, Innovation and Universities (MICINN, https://sede.micinn.gob.es/), project code: RTI2018-094192-R-C22, R.C received this award, both projects were co-funded by The European Regional Development Funds (FEDER) and 3) Plan of Science, Technology and Innovation of the Principality of Asturias, Regional funds PCTI 2018– 2020 (www.ficyt.es/pcti/), project code: IDI2018- 000237), R.C. and F.V. received this award. We acknowledge INIA for the scholarship of Cristina Blanco Va´zquez and Maria Canive. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPublic Library of ScienceSanidad AnimalFacultad de Veterinaria2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236336https://hdl.handle.net/10612/19081reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad de LeónInglésinfo:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/RTA2014-00009-C02-02info:eu-repo/grantAgreement/AEI/ Programa Estatal de I+D+i Orientada a los Retos de la Sociedad / RTI2018-094192-R-C22,http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/190812026-06-24T12:43:27Z
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