{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:09:32Z","timestamp":1780657772185,"version":"3.54.1"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T00:00:00Z","timestamp":1736640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["E-26\/201.330\/2016"],"award-info":[{"award-number":["E-26\/201.330\/2016"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["MR\/X022358\/1"],"award-info":[{"award-number":["MR\/X022358\/1"]}]},{"name":"Medical Research Council Medical Research Council","award":["E-26\/201.330\/2016"],"award-info":[{"award-number":["E-26\/201.330\/2016"]}]},{"name":"Medical Research Council Medical Research Council","award":["MR\/X022358\/1"],"award-info":[{"award-number":["MR\/X022358\/1"]}]},{"name":"NIHR Biomedical Research Centre, Imperial College London","award":["E-26\/201.330\/2016"],"award-info":[{"award-number":["E-26\/201.330\/2016"]}]},{"name":"NIHR Biomedical Research Centre, Imperial College London","award":["MR\/X022358\/1"],"award-info":[{"award-number":["MR\/X022358\/1"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["E-26\/201.330\/2016"],"award-info":[{"award-number":["E-26\/201.330\/2016"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["MR\/X022358\/1"],"award-info":[{"award-number":["MR\/X022358\/1"]}]},{"name":"HUGG-UNIRIO\/EBSERH","award":["E-26\/201.330\/2016"],"award-info":[{"award-number":["E-26\/201.330\/2016"]}]},{"name":"HUGG-UNIRIO\/EBSERH","award":["MR\/X022358\/1"],"award-info":[{"award-number":["MR\/X022358\/1"]}]},{"name":"FAPERJ","award":["E-26\/201.330\/2016"],"award-info":[{"award-number":["E-26\/201.330\/2016"]}]},{"name":"FAPERJ","award":["MR\/X022358\/1"],"award-info":[{"award-number":["MR\/X022358\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background and Objectives: HTLV-1-associated myelopathy (HAM) is a chronic progressive inflammatory disease of the spinal cord. This study assesses the diagnostic accuracy of the neuroinflammatory biomarkers neopterin and cysteine-X-cysteine motif chemokine ligand 10 (CXCL-10) in cerebrospinal fluid (CSF) for HAM. Methods: CSF samples from 75 patients with neurological disorders\u201433 with HAM (Group A), 19 HTLV-1-seronegative with other neuroinflammatory diseases (Group B), and 23 HTLV-1-seronegative with non-neuroinflammatory diseases (Group C)\u2014were retrospectively evaluated. CSF examination included routine analysis, neopterin, and CXCL-10. The diagnostic potential of the biomarkers was evaluated using receiver operating characteristic curves. Results: Higher white cell counts and concentrations of protein, neopterin, and CXCL-10 in CSF were detected in group A (patients with HAM) and group B (p &lt; 0.05). Neopterin showed good accuracy for HAM (A) (cut-off 15 nmol\/L, 80% sensitivity, 74% specificity) and other neuroinflammation (group B) (cut-off 20 nmol\/L, 79% sensitivity, 83% specificity). CXCL-10 demonstrated the highest accuracy in both groups, with Group A (cut-off 110 pg\/mL, 97% sensitivity, 96% specificity) and Group B (cut-off 220 pg\/mL, 100% sensitivity, 100% specificity). Conclusions: Neopterin and CXCL-10 in CSF are accurate biomarkers for detecting neuroinflammation, including HAM. CXCL-10, in particular, is the superior biomarker for both chronic and acute neuroinflammatory diseases.<\/jats:p>","DOI":"10.3390\/v17010089","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T09:49:17Z","timestamp":1736761757000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["CXCL-10 in Cerebrospinal Fluid Detects Neuroinflammation in HTLV-1-Associated Myelopathy with High Accuracy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1978-0548","authenticated-orcid":false,"given":"Samya Jezine","family":"Da Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Doen\u00e7as Infecciosas e Parasit\u00e1rias, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1755-999X","authenticated-orcid":false,"given":"Mauro Jorge","family":"Cabral-Castro","sequence":"additional","affiliation":[{"name":"Departamento de Patologia\u2014Programa de P\u00f3s-Gradua\u00e7\u00e3o em Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Niter\u00f3i 24070-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Claudio","family":"Faria","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de L\u00edquido Cefalorraquidiano, Hospital Universit\u00e1rio Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-5667","authenticated-orcid":false,"given":"Carolina","family":"Rosadas","sequence":"additional","affiliation":[{"name":"Section of Virology, Department of Infectious Disease, Imperial College, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2960-6538","authenticated-orcid":false,"given":"Maria Fernanda Lopes","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Caroline Soares","family":"Dutra","sequence":"additional","affiliation":[{"name":"Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-0345","authenticated-orcid":false,"given":"Yoshihisa","family":"Yamano","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Marianna University School of Medicine, Kawasaki 216-8512, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-2390","authenticated-orcid":false,"given":"Graham","family":"Taylor","sequence":"additional","affiliation":[{"name":"Section of Virology, Department of Infectious Disease, Imperial College, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6007-9142","authenticated-orcid":false,"given":"Marzia","family":"Puccioni-Sohler","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Doen\u00e7as Infecciosas e Parasit\u00e1rias, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil"},{"name":"Laborat\u00f3rio de L\u00edquido Cefalorraquidiano, Hospital Universit\u00e1rio Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil"},{"name":"Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 20270-004, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gessain, A., and Cassar, O. (2012). Epidemiological Aspects and World Distribution of HTLV-1 Infection. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00388"},{"key":"ref_3","first-page":"485","article-title":"HTLV-1 infection: An emerging risk. Pathogenesis, epidemi-ology, diagnosis and associated diseases","volume":"32","author":"Anguita","year":"2019","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12977-019-0499-5","article-title":"Immunovirological biomarkers in HTLV-1-associated myelopathy\/tropical spastic para-paresis (HAM\/TSP)","volume":"16","author":"Jacobson","year":"2019","journal-title":"Retrovirology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1080\/14737175.2023.2272639","article-title":"Advances in the treatment of human T-cell lymphotropic virus type-I associated myelopathy","volume":"23","author":"Mashkani","year":"2023","journal-title":"Expert. Rev. Neurother."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nozuma, S., and Jacobson, S. (2019). Neuroimmunology of Human T-Lymphotropic Virus Type 1-Associated Myelopathy\/Tropical Spastic Paraparesis. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00885"},{"key":"ref_7","unstructured":"Blattner, W. (1990). Review of WHO Kagoshima meeting and diagnostic guidelines for HAM\/TSP. Human Retrovirology: HTLV, Raven Press."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107669","DOI":"10.1016\/j.pharmthera.2020.107669","article-title":"An update on human T-cell leukemia virus type I (HTLV-1)-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) focusing on clinical and laboratory biomarkers","volume":"218","author":"Yamauchi","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122973","DOI":"10.1016\/j.jns.2024.122973","article-title":"HTLV-1 associated myelopathy\/tropical spastic paraparesis (HAM\/TSP): Case based discussion of risk factors, clinical, and therapeutic considerations","volume":"459","author":"Saab","year":"2024","journal-title":"J. Neurol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yamano, Y., and Sato, T. (2012). Clinical pathophysiology of human T-lymphotropic virus-type 1-associated myelopathy\/tropical spastic paraparesis. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00389"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sato, T., Yagishita, N., Tamaki, K., Inoue, E., Hasegawa, D., Nagasaka, M., Suzuki, H., Araya, N., Coler-Reilly, A., and Hasegawa, Y. (2018). Proposal of Classification Criteria for HTLV-1-Associated Myelopathy\/Tropical Spastic Paraparesis Disease Activity. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01651"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Molero-Luis, M., Casas-Alba, D., Orellana, G., Ormazabal, A., Sierra, C., Oliva, C., Valls, A., Velasco, J., Launes, C., and Cuadras, D. (2020). Cerebrospinal fluid neopterin as a biobiomarker of neuroinflammatory diseases. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75500-z"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s12974-018-1366-3","article-title":"High neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan me-tabolites in acute central nervous system infections","volume":"15","author":"Aukrust","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"849","DOI":"10.17219\/acem\/68846","article-title":"CXCL9, CXCL10, CXCL11, and their receptor (CXCR3) in neuroin-flammation and neurodegeneration","volume":"27","author":"Koper","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1017\/S1092852919000981","article-title":"Cerebrospinal fluid biobiomarkers in patients with central nervous system infections: A retrospective study","volume":"25","author":"Alcantarini","year":"2020","journal-title":"CNS Spectr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tamaki, K., Sato, T., Tsugawa, J., Fujioka, S., Yagishita, N., Araya, N., Yamauchi, J., Coler-Reilly, A.L.G., Nagasaka, M., and Hasegawa, Y. (2019). Cerebrospinal Fluid CXCL10 as a Candidate Surrogate Biomarker for HTLV-1-Associated Myelop-athy\/Tropical Spastic Paraparesis. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02110"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Souza, F.D.S., Freitas, N.L., Gomes, Y.C.P., Torres, R.C., Echevarria-Lima, J., da Silva-Filho, I.L., Leite, A.C.C.B., de Lima, M.A.S.D., da Silva, M.T.T., and Ara\u00fajo, A.Q.C. (2021). Following the Clues: Usefulness of Biobiomarkers of Neuroinflammation and Neu-rodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.737941"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.jviromet.2013.07.040","article-title":"Validation of a quantitative real-time PCR assay for HTLV-1 proviral load in peripheral blood mononuclear cells","volume":"193","author":"Rosadas","year":"2013","journal-title":"J. Virol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s13365-020-00881-w","article-title":"Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"26","author":"Nozuma","year":"2020","journal-title":"J. Neurovirol"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Joseph, J., Premeaux, T.A., Tandon, R., Murphy, E.L., Bruhn, R., Nicot, C., Herrera, B.B., Lemenze, A., Alatrash, R., and Baffour Tonto, P. (2024). Dendritic Cells Pulsed with HAM\/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response. Viruses, 16.","DOI":"10.3390\/v16091443"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Puccioni-Sohler, M., da Silva, S.J., Faria, L.C.S., Cabral, D.C.B.I., and Cabral-Castro, M.J. (2021). Neopterin and CXCL-10 in Cerebrospinal Fluid as Potential Biomarkers of Neuroinvasive Dengue and Chikungunya. Pathogens, 10.","DOI":"10.3390\/pathogens10121626"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Da Silva, S.J., Cabral-Castro, M.J., Gon\u00e7alves, C.C.A., Mariani, D., Ferreira, O., Tanuri, A., and Puccioni-Sohler, M. (2024). Challenges in the Diagnosis of SARS-CoV-2 Infection in the Nervous System. Viruses, 16.","DOI":"10.3390\/v16081247"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1089\/aid.2022.0028","article-title":"Human T Lymphotropic Virus 1-Associated Myelopathy: Overview of Human T Cell Lymphotropic Virus-1\/2 Tests and Potential Biomarkers","volume":"38","author":"Poton","year":"2022","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1090","DOI":"10.1212\/NXI.0000000000001090","article-title":"Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1-Associated Myelopathy and Correlates With Neuroinflammation","volume":"8","author":"Rosadas","year":"2021","journal-title":"Neurol. Neu-Roimmunol Neuroinflamm"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.neuint.2013.07.012","article-title":"Temporal expression profile of CXC chemokines in serum of patients with spinal cord injury","volume":"63","author":"Hassanshahi","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s13365-019-00785-4","article-title":"Plasma CXCL10 correlates with HAND in HIV-infected women","volume":"26","author":"Burlacu","year":"2020","journal-title":"J. Neurovirol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1128\/JVI.02007-13","article-title":"Direct, interferon-independent activation of the CXCL10 promoter by NF-\u03baB and interferon regulatory factor 3 during hepatitis C virus infection","volume":"88","author":"Brownell","year":"2014","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1182\/blood-2009-07-231050","article-title":"Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells","volume":"116","author":"Swaims","year":"2010","journal-title":"Blood"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/1\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:27:22Z","timestamp":1759919242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/1\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,12]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["v17010089"],"URL":"https:\/\/doi.org\/10.3390\/v17010089","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,12]]}}}