Author | Freitas, Nicole Lardini | |
Author | Gomes, Yago Côrtes Pinheiro | |
Author | Souza, Flávia dos Santos | |
Author | Torres, Rafael Carvalho | |
Author | Echevarria-Lima, Juliana | |
Author | Leite, Ana Claudia Celestino Bezerra | |
Author | Lima, Marco Antonio Sales Dantas | |
Author | Araújo, Abelardo Queiroz Campos | |
Author | Silva, Marcus Tulius Teixeira | |
Author | Espíndola, Otávio de Melo | |
Access date | 2022-11-17T17:13:14Z | |
Available date | 2022-11-17T17:13:14Z | |
Document date | 2022 | |
Citation | FREITAS, Nicole Lardini et al. Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development. Viruses, v. 14, n. 10, p. 1-18, 2022. | en_US |
ISSN | 1999-4915 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/55678 | |
Language | eng | en_US |
Publisher | MDPI | en_US |
Rights | open access | en_US |
Title | Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development | en_US |
Type | Article | en_US |
DOI | 10.3390/v14102146 | |
Abstract | 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. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Puericultura e Pediatria Martagão Gesteira. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | en_US |
Subject | HAM/TSP | en_US |
Subject | HTLV-1 | en_US |
Subject | IL-18 | en_US |
Subject | Biomarkers | en_US |
Subject | Cerebrospinal fluid | en_US |
Subject | Inflammasome | en_US |
Subject | Neurodegeneration | en_US |