Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression

Detalhes bibliográficos
Autor(a) principal: Souza, Flávia dos Santos
Data de Publicação: 2021
Outros Autores: Freitas, Nicole Lardini, Gomes, Yago Côrtes Pinheiro, Torres, Rafael Carvalho, Echevarria-Lima, Juliana, Silva-Filho, Isaac Lima da, Leite, Ana Claudia Celestino Bezerra, Lima, Marco Antonio Sales Dantas de, Silva, Marcus Tulius Teixeira da, Araújo, Abelardo de Queiroz Campos, Espíndola, Otávio Melo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/50485
Resumo: Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Seção de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.
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spelling Souza, Flávia dos SantosFreitas, Nicole LardiniGomes, Yago Côrtes PinheiroTorres, Rafael CarvalhoEchevarria-Lima, JulianaSilva-Filho, Isaac Lima daLeite, Ana Claudia Celestino BezerraLima, Marco Antonio Sales Dantas deSilva, Marcus Tulius Teixeira daAraújo, Abelardo de Queiroz CamposEspíndola, Otávio Melo2021-12-17T17:45:27Z2021-12-17T17:45:27Z2021SOUZA, Flávia dos Santos et al. Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression. Frontiers in Immunology, v. 12, p. 1-17, 2021.1664-3224https://www.arca.fiocruz.br/handle/icict/5048510.3389/fimmu.2021.737941engFrontiers MediaFollowing the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progressioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Seção de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Plataforma de Imunoanálises. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Puericultura e Pediatria Martagão Gesteira. Serviço de Citometria de Fluxo. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Imunologia Básica e Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Serviço de Neurologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Neurologia Deolindo Couto. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil.Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.HTLV-1Tau proteinBiomarkersCellular prion proteinChemokinesNeopterinNeurofilamentNeuroinflammationinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83099https://www.arca.fiocruz.br/bitstream/icict/50485/1/license.txt586c046dcfeef936e32f0323bb9a47c0MD51ORIGINALFollowing_Flavia_Souza_etal_INI_2021.pdfFollowing_Flavia_Souza_etal_INI_2021.pdfapplication/pdf5629327https://www.arca.fiocruz.br/bitstream/icict/50485/2/Following_Flavia_Souza_etal_INI_2021.pdfd1ea9fa29977be0b040397e1fd4bd2b2MD52icict/504852023-08-15 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dc.title.pt_BR.fl_str_mv Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
title Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
spellingShingle Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
Souza, Flávia dos Santos
HTLV-1
Tau protein
Biomarkers
Cellular prion protein
Chemokines
Neopterin
Neurofilament
Neuroinflammation
title_short Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
title_full Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
title_fullStr Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
title_full_unstemmed Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
title_sort Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
author Souza, Flávia dos Santos
author_facet Souza, Flávia dos Santos
Freitas, Nicole Lardini
Gomes, Yago Côrtes Pinheiro
Torres, Rafael Carvalho
Echevarria-Lima, Juliana
Silva-Filho, Isaac Lima da
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas de
Silva, Marcus Tulius Teixeira da
Araújo, Abelardo de Queiroz Campos
Espíndola, Otávio Melo
author_role author
author2 Freitas, Nicole Lardini
Gomes, Yago Côrtes Pinheiro
Torres, Rafael Carvalho
Echevarria-Lima, Juliana
Silva-Filho, Isaac Lima da
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas de
Silva, Marcus Tulius Teixeira da
Araújo, Abelardo de Queiroz Campos
Espíndola, Otávio Melo
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Souza, Flávia dos Santos
Freitas, Nicole Lardini
Gomes, Yago Côrtes Pinheiro
Torres, Rafael Carvalho
Echevarria-Lima, Juliana
Silva-Filho, Isaac Lima da
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas de
Silva, Marcus Tulius Teixeira da
Araújo, Abelardo de Queiroz Campos
Espíndola, Otávio Melo
dc.subject.en.pt_BR.fl_str_mv HTLV-1
Tau protein
Biomarkers
Cellular prion protein
Chemokines
Neopterin
Neurofilament
Neuroinflammation
topic HTLV-1
Tau protein
Biomarkers
Cellular prion protein
Chemokines
Neopterin
Neurofilament
Neuroinflammation
description Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Neuroinfecções. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Seção de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-12-17T17:45:27Z
dc.date.available.fl_str_mv 2021-12-17T17:45:27Z
dc.date.issued.fl_str_mv 2021
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.citation.fl_str_mv SOUZA, Flávia dos Santos et al. Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression. Frontiers in Immunology, v. 12, p. 1-17, 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/50485
dc.identifier.issn.pt_BR.fl_str_mv 1664-3224
dc.identifier.doi.none.fl_str_mv 10.3389/fimmu.2021.737941
identifier_str_mv SOUZA, Flávia dos Santos et al. Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression. Frontiers in Immunology, v. 12, p. 1-17, 2021.
1664-3224
10.3389/fimmu.2021.737941
url https://www.arca.fiocruz.br/handle/icict/50485
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/50485/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/50485/2/Following_Flavia_Souza_etal_INI_2021.pdf
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