Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1016/j.antiviral.2017.02.001 http://hdl.handle.net/1843/40331 |
Resumo: | In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide. |
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2022-03-22T21:01:15Z2022-03-22T21:01:15Z20171411928https://doi.org/10.1016/j.antiviral.2017.02.00101663542http://hdl.handle.net/1843/40331In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.Neste estudo, foram desenvolvidas estratégias de avaliação de biomarcadores séricos para monitoramento terapêutico de pacientes com HCV. Para este fim, os níveis séricos de quimiocinas/citocinas foram medidos por cytometric-bead-array em pacientes com HCV, categorizados de acordo com a resposta da imunoterapia como: não respondedor/NR, recidivante/REL e sustentado-virológico-respondedor/SVR. Os resultados demonstraram um aumento geral dos níveis séricos de quimiocinas/citocinas em pacientes com HCV. Em geral, a falha terapêutica foi associada à presença de um padrão pró-inflamatório de linha de base predominante com aumento de CCL5/RANTES, IFN-α, IFN-γ juntamente com níveis diminuídos de IL-10 em NR e aumento de IL-6 e TNF em REL. A RVS apresentou um estado pró-inflamatório basal mais baixo com níveis reduzidos de CXCL8/IL-8, IL-12 e IL-17. A incapacidade de manter os níveis de IFN-α durante a imunoterapia foi característica da NR. As assinaturas de quimiocinas/citocinas séricas suportam ainda mais o efeito deletério do estado de linha de base pró-inflamatório e o papel crítico dos níveis de IFN-α aumentados/persistentes para garantir a resposta virológica sustentada. O ambiente pró-inflamatório de linha de base proeminente observado em NR e REL produziu uma rede de biomarcadores restrita com pequeno número de conexões de vizinhança, enquanto SVR exibiu uma rede com conectividade de citocina integrada. Destaca-se que a RVS apresentou uma mudança para um padrão pró-inflamatório na imunoterapia, assumindo um padrão semelhante ao observado em NR e REL na linha de base. Além disso, a imunoterapia orientou o REL para um perfil semelhante ao SVR na linha de base. A análise das alterações da linha de base durante o tratamento apontou o IFN-α e o TNF como biomarcadores de alto desempenho para monitorar o resultado da imunoterapia. Esse conhecimento pode contribuir para novos insights sobre o tratamento e controle da contínua ameaça à saúde pública representada pela infecção pelo HCV em todo o mundo.engUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE MICROBIOLOGIAMED - DEPARTAMENTO DE CLÍNICA MÉDICAAntiviral researchBiomarcadoresQuimiocinasCitocinasHCVIFN-αStrategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseasesEstratégias para avaliação de quimiocinas/citocinas séricas como biomarcadores de resposta terapêutica em pacientes hcv como protótipo para monitorar imunoterapia de doenças infecciosasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.sciencedirect.com/science/article/pii/S016635421630609X?via%3DihubErica GodinhomenezesVanessa Peruhype-magalhãesMaria RiosCaren ChanceyAndréa Teixeira-carvalhoOlindo Assis Martins-filhoRosangela TeixeiraJordana Grazziela Alves Coelho-dos-reisLudmila Melo CardosoÁgata Lopes-ribeiroJuan Jonathan-gonçalvesMarco Túlio Porto GonçalvesRodrigo Dias CambraiaEric Bassetti SoaresLuciana Diniz Silvaapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/40331/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINAL2017_Strategies for serum chemokinecytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases.pdf2017_Strategies for serum chemokinecytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases.pdfapplication/pdf2155778https://repositorio.ufmg.br/bitstream/1843/40331/2/2017_Strategies%20for%20serum%20chemokinecytokine%20assessment%20as%20biomarkers%20of%20therapeutic%20response%20in%20hcv%20patients%20as%20a%20prototype%20to%20monitor%20immunotherapy%20of%20infectious%20diseases.pdf1e8537e044284dc964d2f49bfa352dbfMD521843/403312022-03-22 18:01:15.243oai:repositorio.ufmg.br:1843/40331TElDRU7vv71BIERFIERJU1RSSUJVSe+/ve+/vU8gTu+/vU8tRVhDTFVTSVZBIERPIFJFUE9TSVTvv71SSU8gSU5TVElUVUNJT05BTCBEQSBVRk1HCiAKCkNvbSBhIGFwcmVzZW50Ye+/ve+/vW8gZGVzdGEgbGljZW7vv71hLCB2b2Pvv70gKG8gYXV0b3IgKGVzKSBvdSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGRlIGF1dG9yKSBjb25jZWRlIGFvIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbu+/vW8gZXhjbHVzaXZvIGUgaXJyZXZvZ++/vXZlbCBkZSByZXByb2R1emlyIGUvb3UgZGlzdHJpYnVpciBhIHN1YSBwdWJsaWNh77+977+9byAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0cu+/vW5pY28gZSBlbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mg77+9dWRpbyBvdSB277+9ZGVvLgoKVm9j77+9IGRlY2xhcmEgcXVlIGNvbmhlY2UgYSBwb2zvv710aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2Pvv70gY29uY29yZGEgcXVlIG8gUmVwb3NpdO+/vXJpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250Ze+/vWRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNh77+977+9byBwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHvv73vv71vLgoKVm9j77+9IHRhbWLvv71tIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGPvv71waWEgZGUgc3VhIHB1YmxpY2Hvv73vv71vIHBhcmEgZmlucyBkZSBzZWd1cmFu77+9YSwgYmFjay11cCBlIHByZXNlcnZh77+977+9by4KClZvY++/vSBkZWNsYXJhIHF1ZSBhIHN1YSBwdWJsaWNh77+977+9byDvv70gb3JpZ2luYWwgZSBxdWUgdm9j77+9IHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vu77+9YS4gVm9j77+9IHRhbWLvv71tIGRlY2xhcmEgcXVlIG8gZGVw77+9c2l0byBkZSBzdWEgcHVibGljYe+/ve+/vW8gbu+/vW8sIHF1ZSBzZWphIGRlIHNldSBjb25oZWNpbWVudG8sIGluZnJpbmdlIGRpcmVpdG9zIGF1dG9yYWlzIGRlIG5pbmd177+9bS4KCkNhc28gYSBzdWEgcHVibGljYe+/ve+/vW8gY29udGVuaGEgbWF0ZXJpYWwgcXVlIHZvY++/vSBu77+9byBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2Pvv70gZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc++/vW8gaXJyZXN0cml0YSBkbyBkZXRlbnRvciBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgcGFyYSBjb25jZWRlciBhbyBSZXBvc2l077+9cmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7vv71hLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3Tvv70gY2xhcmFtZW50ZSBpZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBubyBjb250Ze+/vWRvIGRhIHB1YmxpY2Hvv73vv71vIG9yYSBkZXBvc2l0YWRhLgoKQ0FTTyBBIFBVQkxJQ0Hvv73vv71PIE9SQSBERVBPU0lUQURBIFRFTkhBIFNJRE8gUkVTVUxUQURPIERFIFVNIFBBVFJPQ++/vU5JTyBPVSBBUE9JTyBERSBVTUEgQUfvv71OQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0Pvv70gREVDTEFSQSBRVUUgUkVTUEVJVE9VIFRPRE9TIEUgUVVBSVNRVUVSIERJUkVJVE9TIERFIFJFVklT77+9TyBDT01PIFRBTULvv71NIEFTIERFTUFJUyBPQlJJR0Hvv73vv71FUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKTyBSZXBvc2l077+9cmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNh77+977+9bywgZSBu77+9byBmYXLvv70gcXVhbHF1ZXIgYWx0ZXJh77+977+9bywgYWzvv71tIGRhcXVlbGFzIGNvbmNlZGlkYXMgcG9yIGVzdGEgbGljZW7vv71hLgo=Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2022-03-22T21:01:15Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
dc.title.alternative.pt_BR.fl_str_mv |
Estratégias para avaliação de quimiocinas/citocinas séricas como biomarcadores de resposta terapêutica em pacientes hcv como protótipo para monitorar imunoterapia de doenças infecciosas |
title |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
spellingShingle |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases Erica Godinhomenezes Biomarcadores Quimiocinas Citocinas HCV IFN-α |
title_short |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
title_full |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
title_fullStr |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
title_full_unstemmed |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
title_sort |
Strategies for serum chemokine/cytokine assessment as biomarkers of therapeutic response in hcv patients as a prototype to monitor immunotherapy of infectious diseases |
author |
Erica Godinhomenezes |
author_facet |
Erica Godinhomenezes Vanessa Peruhype-magalhães Maria Rios Caren Chancey Andréa Teixeira-carvalho Olindo Assis Martins-filho Rosangela Teixeira Jordana Grazziela Alves Coelho-dos-reis Ludmila Melo Cardoso Ágata Lopes-ribeiro Juan Jonathan-gonçalves Marco Túlio Porto Gonçalves Rodrigo Dias Cambraia Eric Bassetti Soares Luciana Diniz Silva |
author_role |
author |
author2 |
Vanessa Peruhype-magalhães Maria Rios Caren Chancey Andréa Teixeira-carvalho Olindo Assis Martins-filho Rosangela Teixeira Jordana Grazziela Alves Coelho-dos-reis Ludmila Melo Cardoso Ágata Lopes-ribeiro Juan Jonathan-gonçalves Marco Túlio Porto Gonçalves Rodrigo Dias Cambraia Eric Bassetti Soares Luciana Diniz Silva |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Erica Godinhomenezes Vanessa Peruhype-magalhães Maria Rios Caren Chancey Andréa Teixeira-carvalho Olindo Assis Martins-filho Rosangela Teixeira Jordana Grazziela Alves Coelho-dos-reis Ludmila Melo Cardoso Ágata Lopes-ribeiro Juan Jonathan-gonçalves Marco Túlio Porto Gonçalves Rodrigo Dias Cambraia Eric Bassetti Soares Luciana Diniz Silva |
dc.subject.other.pt_BR.fl_str_mv |
Biomarcadores Quimiocinas Citocinas HCV IFN-α |
topic |
Biomarcadores Quimiocinas Citocinas HCV IFN-α |
description |
In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2022-03-22T21:01:15Z |
dc.date.available.fl_str_mv |
2022-03-22T21:01:15Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/40331 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1016/j.antiviral.2017.02.001 |
dc.identifier.issn.pt_BR.fl_str_mv |
01663542 |
url |
https://doi.org/10.1016/j.antiviral.2017.02.001 http://hdl.handle.net/1843/40331 |
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01663542 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Antiviral research |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE MICROBIOLOGIA MED - DEPARTAMENTO DE CLÍNICA MÉDICA |
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Universidade Federal de Minas Gerais |
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