Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP)
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Tipo de documento: | Tese |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da UFMG |
| Texto Completo: | http://hdl.handle.net/1843/BUBD-AD3GCM |
Resumo: | This study aimed at evaluating the biomarkers that may indicate the evolution from the state of asymptomatic carrier (AC) to HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP) based on the serum biomarkers of different clinical stages of HTLV-1-infection. A panel of serum biomarkers was evaluated in samples of 21 blood donors and 87 HTLV-1- infected individuals: 27 AC, 32 putative HAM/TSP (pHAM/TSP) and 28 HAM/TSP. The analyses of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-/IFN-, barely counterbalanced by the regulatory cytocines IL-4/IL-10. The group AC presented a strongly pro-inflammatory/regulatory net, with IL-4/IL-10 playing a central role. Therefore, an immunologic signature of controlled inflammation was characteristic of AC and another of uncontrolled inflammation was typical of HAM/TSP. The biomarkers IL-6 and CystLT were crucial to classify the individual in the spectrum of the disease. These results allowed theconstruction of an algorithm to discriminate AC, pHAM and HAM/TSP based on the selected biomarkers: IFN-, TNF-, IL-10, IL-6, IL-4 and CysLT. Based on the logistic regression, a tree of decision was proposed as a possible strategy to predict the evolution from asymptomatic infection to HAM/TSP, which may be very important in terms of follow-up and future therapeutic decisions. |
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Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP)LeucotrienosQuimiocinasHAM/TSPHTLV-1CitocinasLeucotrienosMedicina QuimiocinasCitocinasVírus 1 linfotrópico T humanoThis study aimed at evaluating the biomarkers that may indicate the evolution from the state of asymptomatic carrier (AC) to HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP) based on the serum biomarkers of different clinical stages of HTLV-1-infection. A panel of serum biomarkers was evaluated in samples of 21 blood donors and 87 HTLV-1- infected individuals: 27 AC, 32 putative HAM/TSP (pHAM/TSP) and 28 HAM/TSP. The analyses of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-/IFN-, barely counterbalanced by the regulatory cytocines IL-4/IL-10. The group AC presented a strongly pro-inflammatory/regulatory net, with IL-4/IL-10 playing a central role. Therefore, an immunologic signature of controlled inflammation was characteristic of AC and another of uncontrolled inflammation was typical of HAM/TSP. The biomarkers IL-6 and CystLT were crucial to classify the individual in the spectrum of the disease. These results allowed theconstruction of an algorithm to discriminate AC, pHAM and HAM/TSP based on the selected biomarkers: IFN-, TNF-, IL-10, IL-6, IL-4 and CysLT. Based on the logistic regression, a tree of decision was proposed as a possible strategy to predict the evolution from asymptomatic infection to HAM/TSP, which may be very important in terms of follow-up and future therapeutic decisions.Este estudo teve como objetivo avaliar biomarcadores na infecção pelo HTLV-1 que possam indicar a evolução da fase assintomática para mielopatia associada ao HTLV-1/paraparesia espática tropical (HAM/TSP) com base no perfil imunológico. Avaliou-se um painel debiomarcadores em 21 amostras de plasma de doadores de sangue e em 87 amostras de plasma de individuos infectados pelo HTLV-1, subdivididos em: 27 portadores assintomáticos (AC), 32 possível HAM (pHAM) e 28 HAM/TSP. A análise das curvas cumulativas e dasassinaturas moleculares demonstrou que o grupo HAM/TSP apresentou um perfil próinflamatório mediado por CXCL10/LTB-4/IL-6/TNF-/IFN-, contrabalançado pelas citocinas regulatórias IL-4/IL-10. O grupo AC apresentou uma rede de correlações próinflamatória/ regulatória fortemente interconectada, com IL-4/IL-10 desempenhando um papelcentral. Assim, delineou-se uma assinatura imunológica de inflamação controlada que caracterizou o AC e outra de inflamação sem controle imunológico que caracterizou a HAM/TSP. Destacaram-se os biomarcadores IL-6 e CysLT como estratégicos na classificaçãodo perfil imunológico do indivíduo no espectro da doença. Esses resultados permitiram a construção de um algoritmo para discriminar os indivíduos AC dos pHAM/TSP e HAM/TSP com base nos biomarcadores: IFN-, TNF-, IL-10, IL-6, IL-4 e CysLT. Com esses resultados, utilizando-se a regressão logística, construiu-se a árvore de decisão que poderá ter valor na predição da evolução de infecção assintomática para mielopatia, sendo muito importante em termos de seguimento dos pacientes e de futuras decisões terapêuticas.Universidade Federal de Minas GeraisUFMGDenise Utsch GoncalvesOlindo de Assis Martins FilhoSimone Kashima HaddadDaniel Gonçalves ChavesSilvana Maria Eloi SantosJuliana de Assis Silva Gomes EstanislauAna Lucia Borges Starling2019-08-12T12:15:28Z2019-08-12T12:15:28Z2016-06-06info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/BUBD-AD3GCMinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2019-11-14T20:48:31Zoai:repositorio.ufmg.br:1843/BUBD-AD3GCMRepositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2019-11-14T20:48:31Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
| dc.title.none.fl_str_mv |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| title |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| spellingShingle |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) Ana Lucia Borges Starling Leucotrienos Quimiocinas HAM/TSP HTLV-1 Citocinas Leucotrienos Medicina Quimiocinas Citocinas Vírus 1 linfotrópico T humano |
| title_short |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| title_full |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| title_fullStr |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| title_full_unstemmed |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| title_sort |
Perfil dos biomarcadores plasmáticos de morbidade na mielopatia associada ao HTLV- 1/paraparesia espástica tropical (HAM/TSP) |
| author |
Ana Lucia Borges Starling |
| author_facet |
Ana Lucia Borges Starling |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Denise Utsch Goncalves Olindo de Assis Martins Filho Simone Kashima Haddad Daniel Gonçalves Chaves Silvana Maria Eloi Santos Juliana de Assis Silva Gomes Estanislau |
| dc.contributor.author.fl_str_mv |
Ana Lucia Borges Starling |
| dc.subject.por.fl_str_mv |
Leucotrienos Quimiocinas HAM/TSP HTLV-1 Citocinas Leucotrienos Medicina Quimiocinas Citocinas Vírus 1 linfotrópico T humano |
| topic |
Leucotrienos Quimiocinas HAM/TSP HTLV-1 Citocinas Leucotrienos Medicina Quimiocinas Citocinas Vírus 1 linfotrópico T humano |
| description |
This study aimed at evaluating the biomarkers that may indicate the evolution from the state of asymptomatic carrier (AC) to HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP) based on the serum biomarkers of different clinical stages of HTLV-1-infection. A panel of serum biomarkers was evaluated in samples of 21 blood donors and 87 HTLV-1- infected individuals: 27 AC, 32 putative HAM/TSP (pHAM/TSP) and 28 HAM/TSP. The analyses of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-/IFN-, barely counterbalanced by the regulatory cytocines IL-4/IL-10. The group AC presented a strongly pro-inflammatory/regulatory net, with IL-4/IL-10 playing a central role. Therefore, an immunologic signature of controlled inflammation was characteristic of AC and another of uncontrolled inflammation was typical of HAM/TSP. The biomarkers IL-6 and CystLT were crucial to classify the individual in the spectrum of the disease. These results allowed theconstruction of an algorithm to discriminate AC, pHAM and HAM/TSP based on the selected biomarkers: IFN-, TNF-, IL-10, IL-6, IL-4 and CysLT. Based on the logistic regression, a tree of decision was proposed as a possible strategy to predict the evolution from asymptomatic infection to HAM/TSP, which may be very important in terms of follow-up and future therapeutic decisions. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016-06-06 2019-08-12T12:15:28Z 2019-08-12T12:15:28Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
| format |
doctoralThesis |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/BUBD-AD3GCM |
| url |
http://hdl.handle.net/1843/BUBD-AD3GCM |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais UFMG |
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Universidade Federal de Minas Gerais UFMG |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
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repositorio@ufmg.br |
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1835272130215804928 |