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Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease...

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Autores principales: Freitas, Nicole Lardini, Gomes, Yago Côrtes Pinheiro, Souza, Flávia dos Santos, Torres, Rafael Carvalho, Echevarria-Lima, Juliana, Leite, Ana Claudia Celestino Bezerra, Lima, Marco Antonio Sales Dantas, Araújo, Abelardo Queiroz Campos, Silva, Marcus Tulius Teixeira, Espíndola, Otávio de Melo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609689/
https://www.ncbi.nlm.nih.gov/pubmed/36298702
http://dx.doi.org/10.3390/v14102146
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author Freitas, Nicole Lardini
Gomes, Yago Côrtes Pinheiro
Souza, Flávia dos Santos
Torres, Rafael Carvalho
Echevarria-Lima, Juliana
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas
Araújo, Abelardo Queiroz Campos
Silva, Marcus Tulius Teixeira
Espíndola, Otávio de Melo
author_facet Freitas, Nicole Lardini
Gomes, Yago Côrtes Pinheiro
Souza, Flávia dos Santos
Torres, Rafael Carvalho
Echevarria-Lima, Juliana
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas
Araújo, Abelardo Queiroz Campos
Silva, Marcus Tulius Teixeira
Espíndola, Otávio de Melo
author_sort Freitas, Nicole Lardini
collection PubMed
description HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, β-NGF, TGF-β1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated β-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-β1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood–brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-β1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.
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spelling pubmed-96096892022-10-28 Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development Freitas, Nicole Lardini Gomes, Yago Côrtes Pinheiro Souza, Flávia dos Santos Torres, Rafael Carvalho Echevarria-Lima, Juliana Leite, Ana Claudia Celestino Bezerra Lima, Marco Antonio Sales Dantas Araújo, Abelardo Queiroz Campos Silva, Marcus Tulius Teixeira Espíndola, Otávio de Melo Viruses Article HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, β-NGF, TGF-β1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated β-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-β1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood–brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-β1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development. MDPI 2022-09-29 /pmc/articles/PMC9609689/ /pubmed/36298702 http://dx.doi.org/10.3390/v14102146 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Freitas, Nicole Lardini
Gomes, Yago Côrtes Pinheiro
Souza, Flávia dos Santos
Torres, Rafael Carvalho
Echevarria-Lima, Juliana
Leite, Ana Claudia Celestino Bezerra
Lima, Marco Antonio Sales Dantas
Araújo, Abelardo Queiroz Campos
Silva, Marcus Tulius Teixeira
Espíndola, Otávio de Melo
Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development
title Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development
title_full Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development
title_fullStr Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development
title_full_unstemmed Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development
title_short Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development
title_sort lessons from the cerebrospinal fluid analysis of htlv-1-infected individuals: biomarkers of inflammation for ham/tsp development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609689/
https://www.ncbi.nlm.nih.gov/pubmed/36298702
http://dx.doi.org/10.3390/v14102146
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