{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:05:26Z","timestamp":1783393526232,"version":"3.54.6"},"reference-count":77,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa INOVA-Novos Talentos-Funda\u00e7\u00e3o Oswaldo Cruz","award":["VPPCB-008-FIO-18-2-39"],"award-info":[{"award-number":["VPPCB-008-FIO-18-2-39"]}]},{"name":"Programa INOVA-Novos Talentos-Funda\u00e7\u00e3o Oswaldo Cruz","award":["INI-003-FIO-19-2-14"],"award-info":[{"award-number":["INI-003-FIO-19-2-14"]}]},{"name":"Programa Jovens Pesquisadores-INI-Funda\u00e7\u00e3o Oswaldo Cruz","award":["VPPCB-008-FIO-18-2-39"],"award-info":[{"award-number":["VPPCB-008-FIO-18-2-39"]}]},{"name":"Programa Jovens Pesquisadores-INI-Funda\u00e7\u00e3o Oswaldo Cruz","award":["INI-003-FIO-19-2-14"],"award-info":[{"award-number":["INI-003-FIO-19-2-14"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES) of the Brazilian Ministry of Education","award":["VPPCB-008-FIO-18-2-39"],"award-info":[{"award-number":["VPPCB-008-FIO-18-2-39"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES) of the Brazilian Ministry of Education","award":["INI-003-FIO-19-2-14"],"award-info":[{"award-number":["INI-003-FIO-19-2-14"]}]},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz","award":["VPPCB-008-FIO-18-2-39"],"award-info":[{"award-number":["VPPCB-008-FIO-18-2-39"]}]},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz","award":["INI-003-FIO-19-2-14"],"award-info":[{"award-number":["INI-003-FIO-19-2-14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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, \u03b2-NGF, TGF-\u03b21, fractalkine\/CX3CL1, IL-6, IL-18, and TNF-\u03b1, 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 &lt;1 and of CXCL10 &lt; 2). HAM\/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated \u03b2-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-\u03b21 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\u2013brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM\/TSP progression, reduced TGF-\u03b21 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.<\/jats:p>","DOI":"10.3390\/v14102146","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T01:43:01Z","timestamp":1664502181000},"page":"2146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM\/TSP Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Nicole Lardini","family":"Freitas","sequence":"first","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-1093","authenticated-orcid":false,"given":"Yago C\u00f4rtes Pinheiro","family":"Gomes","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Instituto Oswaldo Cruz (IOC), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via dos Santos","family":"Souza","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Carvalho","family":"Torres","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"},{"name":"Instituto de Puericultura e Pediatria Martag\u00e3o Gesteira, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-912, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0725-0198","authenticated-orcid":false,"given":"Juliana","family":"Echevarria-Lima","sequence":"additional","affiliation":[{"name":"Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia Celestino Bezerra","family":"Leite","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Antonio Sales Dantas","family":"Lima","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abelardo Queiroz Campos","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4479-4132","authenticated-orcid":false,"given":"Marcus Tulius Teixeira","family":"Silva","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4062-3785","authenticated-orcid":false,"given":"Ot\u00e1vio de Melo","family":"Esp\u00edndola","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas (INI), Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.1038\/sj.onc.1208980","article-title":"History of the Discoveries of the First Human Retroviruses: HTLV-1 and HTLV-2","volume":"24","author":"Gallo","year":"2005","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","article-title":"Epidemiological Aspects and World Distribution of HTLV-1 Infection","volume":"3","author":"Gessain","year":"2012","journal-title":"Front. 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