Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population
Abstract Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either H...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-34757-w |
| _version_ | 1827948151452991488 |
|---|---|
| author | Doris Schor Luís Cristóvão Porto Eric Henrique Roma Julio Castro-Alves Anna Paula Villela Abelardo Q. C. Araújo Maria Glória Bonecini-Almeida |
| author_facet | Doris Schor Luís Cristóvão Porto Eric Henrique Roma Julio Castro-Alves Anna Paula Villela Abelardo Q. C. Araújo Maria Glória Bonecini-Almeida |
| author_sort | Doris Schor |
| collection | DOAJ |
| description | Abstract Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy–Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions. |
| first_indexed | 2024-04-09T12:50:57Z |
| format | Article |
| id | doaj.art-cbd68ff4d68b43a38d9cc841f9f567a9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T12:50:57Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cbd68ff4d68b43a38d9cc841f9f567a92023-05-14T11:15:01ZengNature PortfolioScientific Reports2045-23222023-05-0113111110.1038/s41598-023-34757-wPutative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) populationDoris Schor0Luís Cristóvão Porto1Eric Henrique Roma2Julio Castro-Alves3Anna Paula Villela4Abelardo Q. C. Araújo5Maria Glória Bonecini-Almeida6Laboratório de Imunologia e Imunogenética em Doenças Infecciosas, Instituto Nacional de Infectologia Evandro Chagas-INI/FIOCRUZLaboratório de Histocompatibilidade e Criopreservação, Universidade do Estado do Rio de Janeiro (UERJ)Laboratório de Imunologia e Imunogenética em Doenças Infecciosas, Instituto Nacional de Infectologia Evandro Chagas-INI/FIOCRUZPlataforma de Pesquisa Clínica, Instituto Nacional de Infectologia Evandro Chagas-INI/FIOCRUZLaboratório de Histocompatibilidade e Criopreservação, Universidade do Estado do Rio de Janeiro (UERJ)Laboratório de Pesquisa Clínica em Neuroinfecções, Instituto Nacional de Infectologia Evandro Chagas-INI/FIOCRUZLaboratório de Imunologia e Imunogenética em Doenças Infecciosas, Instituto Nacional de Infectologia Evandro Chagas-INI/FIOCRUZAbstract Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy–Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions.https://doi.org/10.1038/s41598-023-34757-w |
| spellingShingle | Doris Schor Luís Cristóvão Porto Eric Henrique Roma Julio Castro-Alves Anna Paula Villela Abelardo Q. C. Araújo Maria Glória Bonecini-Almeida Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population Scientific Reports |
| title | Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population |
| title_full | Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population |
| title_fullStr | Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population |
| title_full_unstemmed | Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population |
| title_short | Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population |
| title_sort | putative role of hla polymorphism among a brazilian htlv 1 associated myelopathy tropical spastic paraparesis ham tsp population |
| url | https://doi.org/10.1038/s41598-023-34757-w |
| work_keys_str_mv | AT dorisschor putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation AT luiscristovaoporto putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation AT erichenriqueroma putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation AT juliocastroalves putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation AT annapaulavillela putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation AT abelardoqcaraujo putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation AT mariagloriabonecinialmeida putativeroleofhlapolymorphismamongabrazilianhtlv1associatedmyelopathytropicalspasticparaparesishamtsppopulation |