Advances and perspectives of biomarkers in HTLV detection and monitoring: an integrative review
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Published
Feb 29, 2024
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Abstract
Objective: To describe potential HTLV-1 biomarkers for the diagnosis of associated diseases such as ATL and HAM-TSP. Methods: The search was conducted in PubMed Central with articles in English from June 2017 to June 2023, with the descriptors "HTLV-1", "Biomarkers" and "Neuroinflammatory Diseases". After screening titles and abstracts, experimental articles in English that addressed HTLV-1 and laboratory diagnostic biomarkers were selected. Case reports, reviews, commentaries, letters to the editor and out-of-scope articles were excluded. Eligible articles were read in full. Results: Initially 133 articles were found, but only 23 met the inclusion criteria. The main findings included promising biomarkers for the diagnosis of ATL and HAM-TSP, such as CXCL10, neopterin, CHIT1, ANXA1 and genetic polymorphisms of the p75 neurotrophin receptor. Final considerations: This research identified promising biomarkers in HTLV-1 infection and HAM/TSP, such as CXCL10, neopterin, CHIT1, ANXA1 and p75 neurotrophin receptor genetic polymorphisms. However, further studies with larger samples are needed to validate their clinical usefulness in the diagnosis and treatment of these conditions.
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PinheiroR. F., ColaresT. V., Costa Ádria P. de S., LeitãoK. H. S., SilvaJ. C. C. da, PaivaA. G. S. de S., SilvaJ. B. C., CaldasD. dos S., SantosD. K. C. dos, & FernandesC. F. (2024). Advances and perspectives of biomarkers in HTLV detection and monitoring: an integrative review. Electronic Journal Collection Health, 24(2), e15394. https://doi.org/10.25248/reas.e15394.2024
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References
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2. BENENCIO P, et al. HLA-B*35 as a new marker for susceptibility to human T-cell lymphotropic virus type 1 (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in patients living in Argentina. Retrovirology, 2020; 17(1): 29.
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5. DE ASSIS IM, et al. Análise dos níveis de carga proviral em portadores de HTLV-1 com diferentes condições de comprometimento neurológico. Research, Society and Development, 2021; 12(3): e22310313264-e22310313264.
6. DE SOUZA MC e GAGLIANI LH. HTLV–vírus linfotrópico humano: aspectos clínicos, epidemiológico, diagnóstico e controle da doença. UNILUS Ensino e Pesquisa, 2021; 17(49): 132-155.
7. ENOSE-AKAHATA Y e JACOBSON S. Immunovirological markers in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Retrovirology, 2019; 16: 1-14.
8. FLISTER GVS, et al. Prevalência de casos de HTLV entre doadores de sangue no Brasil: uma revisão integrativa. Brazilian Journal of Health Review, 2023; 6(3): 11999-12010.
9. FREITAS NL, et al. Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development. Viruses, 2022; 14(10): 2146.
10. GHOBADI MZ, et al. Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study. Virology journal, 2021; 18(1): 175.
11. GOMES YCP, et al. Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression. Frontiers in immunology, 2022; 13: 949516.
12. IBAÑEZ VR, et al. Basic zipper protein (HBZ): biomarcador diagnóstico y de seguimiento de leucemia/linfoma T del adulto. Revista Cubana de Hematología, Inmunología y Hemoterapia, 2023; 39(1).
13. LEAL FE, et al. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation. Frontiers in microbiology, 2018; 9: 985.
14. LIMA JE, et al. Protein Profile of Blood Monocytes is Altered in HTLV-1 Infected Patients: Implications for HAM/TSP Disease. Scientific reports, 2018; 8(1): 14354.
15. MOHANTY S e HARHAJ EW. Mechanisms of oncogenesis by HTLV-1 Tax. Pathogens, 2020; 9(7): 543.
16. NAITO T, et al. Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP. Retrovirology, 2018; 15(1): 72.
17. NECO HVPC, et al. Mediators Go Together: High Production of CXCL9, CXCL10, IFN-γ, and TNF-α in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis. AIDS research and human retroviruses, 2017; 33(11): 1134-1139.
18. PEREIRA WA e MESQUITA EM. Vírus linfotrópico de células t humana (HTLV): doenças associadas e dificuldades no diagnóstico e tratamento. Rev. Ciênc. Saúde, 2015; 17(1): 40-46.
19. POIESZ BJ, et al. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 1980; 77: 7415-7419.
20. QUEIROZ GAN, et al. Functional capacity of natural killer cells in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. BMC infectious diseases,2019; 19(1): 433.
21. QUEIROZ MAF, et al. Association of the p75NTR Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection. Viruses, 2022; 14(6): 1175.
22. ROCAMONDE B, et al. Immunoprofiling of fresh HAM/TSP blood samples shows altered innate cell responsiveness. PLoS neglected tropical diseases, 2021; 15(11): e0009940.
23. ROSA DV, et al. Plasma and cerebrospinal fluid levels of cytokines as disease markers of neurologic manifestation in long-term HTLV-1 infected individuals. Biomarkers in medicine, 2018; 12(5): 447-454.
24. ROSADAS C, et al. Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: infecção pelo vírus linfotrópico de células T humanas (HTLV). Epidemiologia e Serviços de Saúde, 2021; 30(1): e2020605.
25. ROSADAS, C. et al. Neurofilament light in CSF and plasma is a marker of neuronal damage in HTLV-1–associated myelopathy and correlates with neuroinflammation. Neurology(R) neuroimmunology & neuroinflammation, 2021, 8(6): e1090.
26. SAEIDI M, et al. XCL1, a serum biomarker in neurological diseases; HTLV-1-associated myelopathy and multiple sclerosis. Microbial pathogenesis, 2023; 174: 105962.
27. SAFFARI M, et al. Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2022; 103: 105337.
28. SANTANA BB, et al. Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP. BMC infectious diseases, 2021; 21(1): 219.
29. SANTOS GPM. Estudo de possíveis biomarcadores inflamatórios no plasma de indivíduos vivendo com HTLV-1. Trabalho de conclusão de curso - (Graduação) Universidade Federal do Rio de Janeiro, Instituto de Microbiologia, Bacharel em Ciências Biológicas: Microbiologia e Imunologia, Rio de Janeiro, 2022.
30. SANTOS JLA. Infecção pelo HTLV-1 e progressão para HAM/TSP: contribuição de marcadores moleculares humanos e virais. Tese (Doutorado em Bioquímica e Biologia Molecular) - Universidade Federal da Bahia, Instituto de Ciências da Saúde – ICS, Programa de Pós-Graduação Multicêntrico em Bioquímica e Biologia Molecular, Salvador, 2021.
31. SANTOS TM. Identificação de biomarcadores transcricionais associados às principais manifestações clínicas da infecção pelo HTLV-1. Tese – (Mestrado em Bioquímica e Biologia Molecular), Universidade Federal da Bahia, Instituto de Ciências da Saúde, Programa de Pós-Graduação Multicêntrico em Bioquímica e Biologia Molecular, Salvador, 2020.
32. SATO T, et al. Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity. Frontiers in microbiology, 2018; 9: 1651.
33. SCHIERHOUT G, et al. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. The Lancet Infectious Diseases, 2020; 20(1): 133-143.
34. SCHOR D, et al. Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy/tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil. BMC infectious diseases, 2018; 18(1): 593.
35. SCHRIEFER A e CARVALHO EM. Biomarcadores em medicina. Gazeta Médica da Bahia, 2008; 78(1): 47-51.
36. SOUZA FDS, et al. Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression. Frontiers in immunology, 2021; 12: 737941.
37. TAKENOUCHI N, et al. Expression of TSLC1 in patients with HAM/TSP. Journal of neurovirology, 2023; 26(3): 404-414.
38. TAMAKI K, et al. Cerebrospinal Fluid CXCL10 as a Candidate Surrogate Marker for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis. Frontiers in microbiology,2019; 10: 2110.
39. TOVAR LLANOS V, et al. Mielopatía asociada con infección por HTLV-1: paraparesia espástica tropical. Acta Neurológica Colombiana, 2021; 37(1): 40-46.
2. BENENCIO P, et al. HLA-B*35 as a new marker for susceptibility to human T-cell lymphotropic virus type 1 (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in patients living in Argentina. Retrovirology, 2020; 17(1): 29.
3. CAMPOS KR. Estratégias de melhoria, expansão do diagnóstico e monitoramento das infecções por HTLV-1 e HTLV-2 nas coinfecções por HIV, HBV e HCV. Tese (Doutorado em Ciências) – Secretaria de Estado da Saúde de São Paulo, Programa de Pós-Graduação em Ciências da Coordenadoria de Controle de Doenças, São Paulo, 2020.
4. CAPORALI JFM, et al. Intrarater and interrater agreement and reliability of vestibular evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) for HTLV-1 associated myelopathy testing. PloS one, 2018; 13(9): e0204449.
5. DE ASSIS IM, et al. Análise dos níveis de carga proviral em portadores de HTLV-1 com diferentes condições de comprometimento neurológico. Research, Society and Development, 2021; 12(3): e22310313264-e22310313264.
6. DE SOUZA MC e GAGLIANI LH. HTLV–vírus linfotrópico humano: aspectos clínicos, epidemiológico, diagnóstico e controle da doença. UNILUS Ensino e Pesquisa, 2021; 17(49): 132-155.
7. ENOSE-AKAHATA Y e JACOBSON S. Immunovirological markers in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Retrovirology, 2019; 16: 1-14.
8. FLISTER GVS, et al. Prevalência de casos de HTLV entre doadores de sangue no Brasil: uma revisão integrativa. Brazilian Journal of Health Review, 2023; 6(3): 11999-12010.
9. FREITAS NL, et al. Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development. Viruses, 2022; 14(10): 2146.
10. GHOBADI MZ, et al. Decoding pathogenesis factors involved in the progression of ATLL or HAM/TSP after infection by HTLV-1 through a systems virology study. Virology journal, 2021; 18(1): 175.
11. GOMES YCP, et al. Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression. Frontiers in immunology, 2022; 13: 949516.
12. IBAÑEZ VR, et al. Basic zipper protein (HBZ): biomarcador diagnóstico y de seguimiento de leucemia/linfoma T del adulto. Revista Cubana de Hematología, Inmunología y Hemoterapia, 2023; 39(1).
13. LEAL FE, et al. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation. Frontiers in microbiology, 2018; 9: 985.
14. LIMA JE, et al. Protein Profile of Blood Monocytes is Altered in HTLV-1 Infected Patients: Implications for HAM/TSP Disease. Scientific reports, 2018; 8(1): 14354.
15. MOHANTY S e HARHAJ EW. Mechanisms of oncogenesis by HTLV-1 Tax. Pathogens, 2020; 9(7): 543.
16. NAITO T, et al. Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP. Retrovirology, 2018; 15(1): 72.
17. NECO HVPC, et al. Mediators Go Together: High Production of CXCL9, CXCL10, IFN-γ, and TNF-α in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis. AIDS research and human retroviruses, 2017; 33(11): 1134-1139.
18. PEREIRA WA e MESQUITA EM. Vírus linfotrópico de células t humana (HTLV): doenças associadas e dificuldades no diagnóstico e tratamento. Rev. Ciênc. Saúde, 2015; 17(1): 40-46.
19. POIESZ BJ, et al. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 1980; 77: 7415-7419.
20. QUEIROZ GAN, et al. Functional capacity of natural killer cells in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. BMC infectious diseases,2019; 19(1): 433.
21. QUEIROZ MAF, et al. Association of the p75NTR Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection. Viruses, 2022; 14(6): 1175.
22. ROCAMONDE B, et al. Immunoprofiling of fresh HAM/TSP blood samples shows altered innate cell responsiveness. PLoS neglected tropical diseases, 2021; 15(11): e0009940.
23. ROSA DV, et al. Plasma and cerebrospinal fluid levels of cytokines as disease markers of neurologic manifestation in long-term HTLV-1 infected individuals. Biomarkers in medicine, 2018; 12(5): 447-454.
24. ROSADAS C, et al. Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: infecção pelo vírus linfotrópico de células T humanas (HTLV). Epidemiologia e Serviços de Saúde, 2021; 30(1): e2020605.
25. ROSADAS, C. et al. Neurofilament light in CSF and plasma is a marker of neuronal damage in HTLV-1–associated myelopathy and correlates with neuroinflammation. Neurology(R) neuroimmunology & neuroinflammation, 2021, 8(6): e1090.
26. SAEIDI M, et al. XCL1, a serum biomarker in neurological diseases; HTLV-1-associated myelopathy and multiple sclerosis. Microbial pathogenesis, 2023; 174: 105962.
27. SAFFARI M, et al. Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2022; 103: 105337.
28. SANTANA BB, et al. Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP. BMC infectious diseases, 2021; 21(1): 219.
29. SANTOS GPM. Estudo de possíveis biomarcadores inflamatórios no plasma de indivíduos vivendo com HTLV-1. Trabalho de conclusão de curso - (Graduação) Universidade Federal do Rio de Janeiro, Instituto de Microbiologia, Bacharel em Ciências Biológicas: Microbiologia e Imunologia, Rio de Janeiro, 2022.
30. SANTOS JLA. Infecção pelo HTLV-1 e progressão para HAM/TSP: contribuição de marcadores moleculares humanos e virais. Tese (Doutorado em Bioquímica e Biologia Molecular) - Universidade Federal da Bahia, Instituto de Ciências da Saúde – ICS, Programa de Pós-Graduação Multicêntrico em Bioquímica e Biologia Molecular, Salvador, 2021.
31. SANTOS TM. Identificação de biomarcadores transcricionais associados às principais manifestações clínicas da infecção pelo HTLV-1. Tese – (Mestrado em Bioquímica e Biologia Molecular), Universidade Federal da Bahia, Instituto de Ciências da Saúde, Programa de Pós-Graduação Multicêntrico em Bioquímica e Biologia Molecular, Salvador, 2020.
32. SATO T, et al. Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity. Frontiers in microbiology, 2018; 9: 1651.
33. SCHIERHOUT G, et al. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. The Lancet Infectious Diseases, 2020; 20(1): 133-143.
34. SCHOR D, et al. Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy/tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil. BMC infectious diseases, 2018; 18(1): 593.
35. SCHRIEFER A e CARVALHO EM. Biomarcadores em medicina. Gazeta Médica da Bahia, 2008; 78(1): 47-51.
36. SOUZA FDS, et al. Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression. Frontiers in immunology, 2021; 12: 737941.
37. TAKENOUCHI N, et al. Expression of TSLC1 in patients with HAM/TSP. Journal of neurovirology, 2023; 26(3): 404-414.
38. TAMAKI K, et al. Cerebrospinal Fluid CXCL10 as a Candidate Surrogate Marker for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis. Frontiers in microbiology,2019; 10: 2110.
39. TOVAR LLANOS V, et al. Mielopatía asociada con infección por HTLV-1: paraparesia espástica tropical. Acta Neurológica Colombiana, 2021; 37(1): 40-46.