Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
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 neu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.737941/full |
| _version_ | 1819111641788186624 |
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| author | Flávia dos Santos Souza Flávia dos Santos Souza Nicole Lardini Freitas Yago Côrtes Pinheiro Gomes Rafael Carvalho Torres Rafael Carvalho Torres Juliana Echevarria-Lima Isaac Lima da Silva-Filho Ana Claudia Celestino Bezerra Leite Marco Antonio Sales Dantas de Lima Marco Antonio Sales Dantas de Lima Marcus Tulius Teixeira da Silva Abelardo de Queiroz Campos Araújo Abelardo de Queiroz Campos Araújo Otávio Melo Espíndola |
| author_facet | Flávia dos Santos Souza Flávia dos Santos Souza Nicole Lardini Freitas Yago Côrtes Pinheiro Gomes Rafael Carvalho Torres Rafael Carvalho Torres Juliana Echevarria-Lima Isaac Lima da Silva-Filho Ana Claudia Celestino Bezerra Leite Marco Antonio Sales Dantas de Lima Marco Antonio Sales Dantas de Lima Marcus Tulius Teixeira da Silva Abelardo de Queiroz Campos Araújo Abelardo de Queiroz Campos Araújo Otávio Melo Espíndola |
| author_sort | Flávia dos Santos Souza |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T04:00:51Z |
| format | Article |
| id | doaj.art-31b511d1838f4301908a7862c043e77d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T04:00:51Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-31b511d1838f4301908a7862c043e77d2022-12-21T18:39:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.737941737941Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy ProgressionFlávia dos Santos Souza0Flávia dos Santos Souza1Nicole Lardini Freitas2Yago Côrtes Pinheiro Gomes3Rafael Carvalho Torres4Rafael Carvalho Torres5Juliana Echevarria-Lima6Isaac Lima da Silva-Filho7Ana Claudia Celestino Bezerra Leite8Marco Antonio Sales Dantas de Lima9Marco Antonio Sales Dantas de Lima10Marcus Tulius Teixeira da Silva11Abelardo de Queiroz Campos Araújo12Abelardo de Queiroz Campos Araújo13Otávio Melo Espíndola14Laboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilSeção de Imunodiagnóstico, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilPlataforma de Imunoanálises, Instituto de Biofísica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilServiço de Citometria de Fluxo, Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilLaboratório de Imunologia Básica e Aplicada, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilServiço de Neurologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilInstituto de Neurologia Deolindo Couto (INDC), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilLaboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, BrazilHuman 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.737941/fullHTLV-1biomarkersneuroinflammationneopterinchemokinesTau protein |
| spellingShingle | Flávia dos Santos Souza Flávia dos Santos Souza Nicole Lardini Freitas Yago Côrtes Pinheiro Gomes Rafael Carvalho Torres Rafael Carvalho Torres Juliana Echevarria-Lima Isaac Lima da Silva-Filho Ana Claudia Celestino Bezerra Leite Marco Antonio Sales Dantas de Lima Marco Antonio Sales Dantas de Lima Marcus Tulius Teixeira da Silva Abelardo de Queiroz Campos Araújo Abelardo de Queiroz Campos Araújo Otávio Melo Espíndola Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression Frontiers in Immunology HTLV-1 biomarkers neuroinflammation neopterin chemokines Tau protein |
| title | 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_short | 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 |
| topic | HTLV-1 biomarkers neuroinflammation neopterin chemokines Tau protein |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.737941/full |
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