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Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients

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Resumo:Background: Invasive pulmonary aspergillosis (IPA) is an infection that primarily affects immunocompromised hosts, including hematological patients and stem-cell transplant recipients. The diagnosis of IPA remains challenging, making desirable the availability of new specific biomarkers. High-throughput methods now allow us to interrogate the immune system for multiple markers of inflammation with enhanced resolution.Methods: To determine whether a signature of alveolar cytokines could be associated with the development of IPA and used as a diagnostic biomarker, we performed a nested case-control study involving 113 patients at-risk.Results: Among the 32 analytes tested, IL-beta, IL-6, IL-8, IL-17A, IL-23, and TNF a were significantly increased among patients with IPA, defining two clusters able to accurately differentiate cases of infection from controls. Genetic variants previously reported to confer increased risk of IPA compromised the production of specific cytokines and impaired their discriminatory potential toward infection. Collectively, our data indicated that IL-8 was the best performing cytokine, with alveolar levels >= 904 pg/mL predicting IPA with elevated sensitivity (90%), specificity (73%), and negative predictive value (88%).Conclusions: These findings highlight the existence of a specific profile of alveolar cytokines, with IL-8 being the dominant discriminator, whichmight be useful in supporting current diagnostic approaches for IPA.
Autores principais:Gonçalves, Samuel Martins
Outros Autores:Lagrou, Katrien; Rodrigues, Claudia S.; Campos, Claudia F.; Bernal-Martinez, Leticia; Rodrigues, Fernando José dos Santos; Silvestre, Ricardo Jorge Leal; Alcazar-Fuoli, Laura; Maertens, Johan A.; Cunha, Cristina; Carvalho, Agostinho
Assunto:Invasive pulmonary aspergillosis Biomarkers Cytokines/chemokines Bronchoalveolar lavage Fungal diagnostics
Ano:2017
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
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author Gonçalves, Samuel Martins
author2 Lagrou, Katrien
Rodrigues, Claudia S.
Campos, Claudia F.
Bernal-Martinez, Leticia
Rodrigues, Fernando José dos Santos
Silvestre, Ricardo Jorge Leal
Alcazar-Fuoli, Laura
Maertens, Johan A.
Cunha, Cristina
Carvalho, Agostinho
author2_role author
author
author
author
author
author
author
author
author
author
author_facet Gonçalves, Samuel Martins
Lagrou, Katrien
Rodrigues, Claudia S.
Campos, Claudia F.
Bernal-Martinez, Leticia
Rodrigues, Fernando José dos Santos
Silvestre, Ricardo Jorge Leal
Alcazar-Fuoli, Laura
Maertens, Johan A.
Cunha, Cristina
Carvalho, Agostinho
author_role author
contributor_name_str_mv Universidade do Minho
country_str PT
creators_json_txt [{\"Person.name\":\"Gonçalves, Samuel Martins\"},{\"Person.name\":\"Lagrou, Katrien\"},{\"Person.name\":\"Rodrigues, Claudia S.\"},{\"Person.name\":\"Campos, Claudia F.\"},{\"Person.name\":\"Bernal-Martinez, Leticia\"},{\"Person.name\":\"Rodrigues, Fernando José dos Santos\"},{\"Person.name\":\"Silvestre, Ricardo Jorge Leal\"},{\"Person.name\":\"Alcazar-Fuoli, Laura\"},{\"Person.name\":\"Maertens, Johan A.\"},{\"Person.name\":\"Cunha, Cristina\"},{\"Person.name\":\"Carvalho, Agostinho\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Universidade do Minho
datacite.creators.creator.creatorName.fl_str_mv Gonçalves, Samuel Martins
Lagrou, Katrien
Rodrigues, Claudia S.
Campos, Claudia F.
Bernal-Martinez, Leticia
Rodrigues, Fernando José dos Santos
Silvestre, Ricardo Jorge Leal
Alcazar-Fuoli, Laura
Maertens, Johan A.
Cunha, Cristina
Carvalho, Agostinho
datacite.date.Accepted.fl_str_mv 2017-11-29T00:00:00Z
datacite.date.available.fl_str_mv 2018-02-09T12:05:58Z
datacite.date.embargoed.fl_str_mv 2018-02-09T12:05:58Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv Invasive pulmonary aspergillosis
Biomarkers
Cytokines/chemokines
Bronchoalveolar lavage
Fungal diagnostics
datacite.titles.title.fl_str_mv Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
dc.contributor.none.fl_str_mv Universidade do Minho
dc.creator.none.fl_str_mv Gonçalves, Samuel Martins
Lagrou, Katrien
Rodrigues, Claudia S.
Campos, Claudia F.
Bernal-Martinez, Leticia
Rodrigues, Fernando José dos Santos
Silvestre, Ricardo Jorge Leal
Alcazar-Fuoli, Laura
Maertens, Johan A.
Cunha, Cristina
Carvalho, Agostinho
dc.date.Accepted.fl_str_mv 2017-11-29T00:00:00Z
dc.date.available.fl_str_mv 2018-02-09T12:05:58Z
dc.date.embargoed.fl_str_mv 2018-02-09T12:05:58Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv https://hdl.handle.net/1822/50276
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Frontiers Media
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv Invasive pulmonary aspergillosis
Biomarkers
Cytokines/chemokines
Bronchoalveolar lavage
Fungal diagnostics
dc.title.fl_str_mv Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Background: Invasive pulmonary aspergillosis (IPA) is an infection that primarily affects immunocompromised hosts, including hematological patients and stem-cell transplant recipients. The diagnosis of IPA remains challenging, making desirable the availability of new specific biomarkers. High-throughput methods now allow us to interrogate the immune system for multiple markers of inflammation with enhanced resolution.Methods: To determine whether a signature of alveolar cytokines could be associated with the development of IPA and used as a diagnostic biomarker, we performed a nested case-control study involving 113 patients at-risk.Results: Among the 32 analytes tested, IL-beta, IL-6, IL-8, IL-17A, IL-23, and TNF a were significantly increased among patients with IPA, defining two clusters able to accurately differentiate cases of infection from controls. Genetic variants previously reported to confer increased risk of IPA compromised the production of specific cytokines and impaired their discriminatory potential toward infection. Collectively, our data indicated that IL-8 was the best performing cytokine, with alveolar levels >= 904 pg/mL predicting IPA with elevated sensitivity (90%), specificity (73%), and negative predictive value (88%).Conclusions: These findings highlight the existence of a specific profile of alveolar cytokines, with IL-8 being the dominant discriminator, whichmight be useful in supporting current diagnostic approaches for IPA.
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eu_rights_str_mv openAccess
format article
fulltext.url.fl_str_mv https://prod-dspace.uminho.pt/bitstreams/9c653ea7-7296-4186-8401-4eeefa28a3ed/download
id rum_34cece6df3ce233bdebd4a2cdf06002f
identifier.url.fl_str_mv https://hdl.handle.net/1822/50276
instacron_str repositorium
institution Universidade do Minho
instname_str Universidade do Minho
language eng
network_acronym_str rum
network_name_str RepositóriUM - Universidade do Minho
oai_identifier_str oai:repositorium.uminho.pt:1822/50276
organization_str_mv urn:organizationAcronym:repositorium
person_str_mv Gonçalves, Samuel Martins
Lagrou, Katrien
Rodrigues, Claudia S.
Campos, Claudia F.
Bernal-Martinez, Leticia
Rodrigues, Fernando José dos Santos
Silvestre, Ricardo Jorge Leal
Alcazar-Fuoli, Laura
Maertens, Johan A.
Cunha, Cristina
Carvalho, Agostinho
publishDate 2017
publisher.none.fl_str_mv Frontiers Media
reponame_str RepositóriUM - Universidade do Minho
repository_id_str urn:repositoryAcronym:rum
service_str_mv urn:repositoryAcronym:rum
spelling engFrontiers MediaporBackground: Invasive pulmonary aspergillosis (IPA) is an infection that primarily affects immunocompromised hosts, including hematological patients and stem-cell transplant recipients. The diagnosis of IPA remains challenging, making desirable the availability of new specific biomarkers. High-throughput methods now allow us to interrogate the immune system for multiple markers of inflammation with enhanced resolution.Methods: To determine whether a signature of alveolar cytokines could be associated with the development of IPA and used as a diagnostic biomarker, we performed a nested case-control study involving 113 patients at-risk.Results: Among the 32 analytes tested, IL-beta, IL-6, IL-8, IL-17A, IL-23, and TNF a were significantly increased among patients with IPA, defining two clusters able to accurately differentiate cases of infection from controls. Genetic variants previously reported to confer increased risk of IPA compromised the production of specific cytokines and impaired their discriminatory potential toward infection. Collectively, our data indicated that IL-8 was the best performing cytokine, with alveolar levels >= 904 pg/mL predicting IPA with elevated sensitivity (90%), specificity (73%), and negative predictive value (88%).Conclusions: These findings highlight the existence of a specific profile of alveolar cytokines, with IL-8 being the dominant discriminator, whichmight be useful in supporting current diagnostic approaches for IPA.application/pdfporEvaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk PatientsGonçalves, Samuel MartinsLagrou, KatrienRodrigues, Claudia S.Campos, Claudia F.Bernal-Martinez, LeticiaRodrigues, Fernando José dos SantosSilvestre, Ricardo Jorge LealAlcazar-Fuoli, LauraMaertens, Johan A.Cunha, CristinaCarvalho, AgostinhoHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf1664-302XDOIIsPartOf10.3389/fmicb.2017.023622018-02-09T12:05:58Z2017-11-292018-01-16T16:30:56Z2017-11-29T00:00:00ZHandlehttps://hdl.handle.net/1822/50276http://purl.org/coar/access_right/c_abf2open accessInvasive pulmonary aspergillosisBiomarkersCytokines/chemokinesBronchoalveolar lavageFungal diagnostics4474140 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/9c653ea7-7296-4186-8401-4eeefa28a3ed/download
spellingShingle Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
Gonçalves, Samuel Martins
Invasive pulmonary aspergillosis
Biomarkers
Cytokines/chemokines
Bronchoalveolar lavage
Fungal diagnostics
status SINGLETON
subject.fl_str_mv Invasive pulmonary aspergillosis
Biomarkers
Cytokines/chemokines
Bronchoalveolar lavage
Fungal diagnostics
title Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
title_full Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
title_fullStr Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
title_full_unstemmed Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
title_short Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
title_sort Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients
topic Invasive pulmonary aspergillosis
Biomarkers
Cytokines/chemokines
Bronchoalveolar lavage
Fungal diagnostics
topic_facet Invasive pulmonary aspergillosis
Biomarkers
Cytokines/chemokines
Bronchoalveolar lavage
Fungal diagnostics
url https://hdl.handle.net/1822/50276
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