Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression
Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.949516/full |
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| author | Yago Côrtes Pinheiro Gomes Yago Côrtes Pinheiro Gomes Nicole Lardini Freitas Flávia Santos Souza Vanessa Sandim Denise Abreu Pereira Fábio César Sousa Nogueira Fábio César Sousa Nogueira Juliana Echevarria-Lima Ana Claudia Celestino Bezerra Leite Marco Antonio Sales Dantas Lima Marcus Tulius Teixeira Silva Abelardo Queiroz Campos Araújo Ana Carolina Paulo Vicente Otávio Melo Espíndola |
| author_facet | Yago Côrtes Pinheiro Gomes Yago Côrtes Pinheiro Gomes Nicole Lardini Freitas Flávia Santos Souza Vanessa Sandim Denise Abreu Pereira Fábio César Sousa Nogueira Fábio César Sousa Nogueira Juliana Echevarria-Lima Ana Claudia Celestino Bezerra Leite Marco Antonio Sales Dantas Lima Marcus Tulius Teixeira Silva Abelardo Queiroz Campos Araújo Ana Carolina Paulo Vicente Otávio Melo Espíndola |
| author_sort | Yago Côrtes Pinheiro Gomes |
| collection | DOAJ |
| description | Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis. |
| first_indexed | 2024-04-13T13:18:43Z |
| format | Article |
| id | doaj.art-bda781c3e89a4378a47a606b01fd1f34 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T13:18:43Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bda781c3e89a4378a47a606b01fd1f342022-12-22T02:45:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.949516949516Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progressionYago Côrtes Pinheiro Gomes0Yago Côrtes Pinheiro Gomes1Nicole Lardini Freitas2Flávia Santos Souza3Vanessa Sandim4Denise Abreu Pereira5Fábio César Sousa Nogueira6Fábio César Sousa Nogueira7Juliana Echevarria-Lima8Ana Claudia Celestino Bezerra Leite9Marco Antonio Sales Dantas Lima10Marcus Tulius Teixeira Silva11Abelardo Queiroz Campos Araújo12Ana Carolina Paulo Vicente13Otávio Melo Espíndola14Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilOswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilInstitute of Medical Biochemistry Leopoldo de Meis (IBqM), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilProgram of Cellular and Molecular Oncobiology (POCM), National Institute of Cancer (INCA), Rio de Janeiro, BrazilLaboratory of Proteomics, Laboratory for the Support of Technological Development (LADETEC), Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilProteomics Unit, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilInstitute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilOswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilEvandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, BrazilHuman T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.949516/fullHTLV-1HAM/TSPbiomarkerscerebrospinal fluidneurodegenerationchitotriosidase 1 |
| spellingShingle | Yago Côrtes Pinheiro Gomes Yago Côrtes Pinheiro Gomes Nicole Lardini Freitas Flávia Santos Souza Vanessa Sandim Denise Abreu Pereira Fábio César Sousa Nogueira Fábio César Sousa Nogueira Juliana Echevarria-Lima Ana Claudia Celestino Bezerra Leite Marco Antonio Sales Dantas Lima Marcus Tulius Teixeira Silva Abelardo Queiroz Campos Araújo Ana Carolina Paulo Vicente Otávio Melo Espíndola Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression Frontiers in Immunology HTLV-1 HAM/TSP biomarkers cerebrospinal fluid neurodegeneration chitotriosidase 1 |
| title | Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression |
| title_full | Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression |
| title_fullStr | Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression |
| title_full_unstemmed | Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression |
| title_short | Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression |
| title_sort | chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for htlv 1 associated myelopathy tropical spastic paraparesis ham tsp progression |
| topic | HTLV-1 HAM/TSP biomarkers cerebrospinal fluid neurodegeneration chitotriosidase 1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.949516/full |
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