Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts

Detalhes bibliográficos
Autor(a) principal: Marçal, Pedro Henrique Ferreira
Data de Publicação: 2020
Outros Autores: Gama, Rafael Silva, Oliveira, Lorena Bruna Pereira de, Martins Filho, Olindo Assis, Pinheiro, Roberta Olmo, Sarno, Euzenir Nunes, Moraes, Milton Ozório, Fraga, Lucia Alves de Oliveira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
DOI: 10.1186/s40249-020-00763-7
Texto Completo: https://www.arca.fiocruz.br/handle/icict/58628
Resumo: Universidade Vale do Rio Doce. Governador Valadares, MG, Brazil.
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spelling Marçal, Pedro Henrique FerreiraGama, Rafael SilvaOliveira, Lorena Bruna Pereira deMartins Filho, Olindo AssisPinheiro, Roberta OlmoSarno, Euzenir NunesMoraes, Milton OzórioFraga, Lucia Alves de Oliveira2023-05-24T17:42:52Z2023-05-24T17:42:52Z2020MARÇAL, Pedro Henrique Ferreira et al. Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts. Infect Dis Poverty, v. 9, n. 1, 167, 2020. doi: 10.1186/s40249-020-00763-7.2049-9957https://www.arca.fiocruz.br/handle/icict/5862810.1186/s40249-020-00763-7engBioMed CentralFunctional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contactsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Vale do Rio Doce. Governador Valadares, MG, Brazil.Universidade Vale do Rio Doce. Governador Valadares, MG, Brazil.Universidade Vale do Rio Doce. Governador Valadares, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Universidade Federal de Juiz de Fora. Instituto de Ciências da Vida.Núcleo de Pesquisa em Hansenologia. Governador Valadares, MG, Brazil.Background Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: paucibacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts. Methods The cross-sectional study enrolled 49 participants, including 19 patients and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated in the presence of Mycobacterium leprae bacilli. The cells were prepared for surface (CD4(+) and CD8(+)) and intracytoplasmic cytokine staining (IFN-gamma, IL-4 and IL-10). Multiple comparisons amongst groups were carried out by ANOVA, Kruskal-Wallis, Student T or Mann-Whitney test. Comparative analysis of categorical variables was performed by Chi-square. Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker levels. Results The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-gamma(+) T-cell subsets along with IL-10(+) and IL-4(+) from CD4(+) T-cells, as compared to health Controls (Venn diagram report). Moreover, statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons, according to the data normality distribution. L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-gamma(+), IL-10(+) and IL-4(+) produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10(+) and IL-4(+) T-cells with minor contribution of IFN-gamma produced by CD4(+) T-cells. Noteworthy was that HHC(MB) exhibited enhanced frequency of IFN-gamma(+) T-cells, contrasting with HHC(PB) that presented a cytokine profile limited to IL-10 and IL-4. Conclusions Our data demonstrated that L(PB) displayed enhanced percentage of IFN-gamma(+), IL-10(+) and IL-4(+) as compared to L(MB) that presented functional profile mediated by IL-10(+) and IL-4(+) T-cells and HHC(MB) exhibited enhanced frequency of IFN-gamma(+) T-cells, contrasting with HHC(PB). Together, our findings provide additional immunological features associated with leprosy and household contacts. These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.LeprosyMycobacterium lepraeCytokinesHousehold contactsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALFunctional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts.pdfFunctional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts.pdfapplication/pdf1870375https://www.arca.fiocruz.br/bitstream/icict/58628/2/Functional%20biomarker%20signatures%20of%20circulating%20T-cells%20and%20its%20association%20with%20distinct%20clinical%20status%20of%20leprosy%20patients%20and%20their%20respective%20household%20contacts.pdf890645e2b77bc4d0ce903fd3fc704a30MD52LICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/58628/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51icict/586282023-05-24 14:42:53.733oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-05-24T17:42:53Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
title Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
spellingShingle Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
Marçal, Pedro Henrique Ferreira
Leprosy
Mycobacterium leprae
Cytokines
Household contacts
title_short Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
title_full Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
title_fullStr Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
title_full_unstemmed Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
title_sort Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
author Marçal, Pedro Henrique Ferreira
author_facet Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Martins Filho, Olindo Assis
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Moraes, Milton Ozório
Fraga, Lucia Alves de Oliveira
author_role author
author2 Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Martins Filho, Olindo Assis
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Moraes, Milton Ozório
Fraga, Lucia Alves de Oliveira
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Marçal, Pedro Henrique Ferreira
Gama, Rafael Silva
Oliveira, Lorena Bruna Pereira de
Martins Filho, Olindo Assis
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Moraes, Milton Ozório
Fraga, Lucia Alves de Oliveira
dc.subject.en.en_US.fl_str_mv Leprosy
Mycobacterium leprae
Cytokines
Household contacts
topic Leprosy
Mycobacterium leprae
Cytokines
Household contacts
description Universidade Vale do Rio Doce. Governador Valadares, MG, Brazil.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2023-05-24T17:42:52Z
dc.date.available.fl_str_mv 2023-05-24T17:42:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv MARÇAL, Pedro Henrique Ferreira et al. Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts. Infect Dis Poverty, v. 9, n. 1, 167, 2020. doi: 10.1186/s40249-020-00763-7.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/58628
dc.identifier.issn.en_US.fl_str_mv 2049-9957
dc.identifier.doi.none.fl_str_mv 10.1186/s40249-020-00763-7
identifier_str_mv MARÇAL, Pedro Henrique Ferreira et al. Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts. Infect Dis Poverty, v. 9, n. 1, 167, 2020. doi: 10.1186/s40249-020-00763-7.
2049-9957
10.1186/s40249-020-00763-7
url https://www.arca.fiocruz.br/handle/icict/58628
dc.language.iso.fl_str_mv eng
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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