Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , |
| 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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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. |
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2021 |
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2021-12-17T17:45:27Z |
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2021-12-17T17:45:27Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/50485 |
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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 |
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Frontiers Media |
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Frontiers Media |
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