Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression
IntroductionThe envelope proteins syncytin-1 and pHERV-W from the Human Endogenous Retroviral family ‘W’ (HERV-W) have been identified as potential risk factors in multiple sclerosis (MS). This study aims to evaluate both humoral and cell-mediated immune response to antigenic peptides derived from t...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505239/full |
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| author | Stefano Ruberto Stefano Ruberto María I. Domınguez-Mozo M. Angel Garcıa-Martınez Davide Cossu Davide Cossu Leonardo A. Sechi Leonardo A. Sechi Roberto Alvarez-Lafuente |
| author_facet | Stefano Ruberto Stefano Ruberto María I. Domınguez-Mozo M. Angel Garcıa-Martınez Davide Cossu Davide Cossu Leonardo A. Sechi Leonardo A. Sechi Roberto Alvarez-Lafuente |
| author_sort | Stefano Ruberto |
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| description | IntroductionThe envelope proteins syncytin-1 and pHERV-W from the Human Endogenous Retroviral family ‘W’ (HERV-W) have been identified as potential risk factors in multiple sclerosis (MS). This study aims to evaluate both humoral and cell-mediated immune response to antigenic peptides derived from these proteins across different clinical forms and inflammatory phases of MS.MethodsIndirect enzyme-linked immunosorbent assay (ELISA) was employed to measure immunoglobulin G (IgG) responses to syncytin-1env 486-500 and pHERV-Wenv 486-504 peptides in MS patients. Discriminant analysis was used to assess whether clinical course prediction could be enhanced by integrating clinical variables with humoral response data against other MS-associated viral factors. Additionally, peripheral blood mononuclear cells from MS patients and healthy controls (HC) were analyzed for inflammatory responses following stimulation with these peptides.ResultsMS patients exhibited significantly elevated antibody titers against -pHERV-Wenv 486-504 and syncytin-1env 486-500 compared to HCs, with the highest levels observed in progressive MS forms. Discriminant analysis accurately predicted the clinical course in 75.3% of the cases, with an 85% accuracy rate for progressive MS. In vitro, stimulation with pHERV-Wenv 486-504 led to a notable increase in pro-inflammatory cytokine production by CD4, CD8, and CD19 cells compared to syncytin-1env 486-500. A strong correlation was found between pHERV- Wenv 486-504 induced cytokine production and EBV and CMV titers in MS patients.DiscussionThese findings suggest that the pHERV-W envelope protein could be a valuable biomarker for monitoring peripheral inflammation in MS. |
| format | Article |
| id | doaj-art-06f7ba557e5e4926ba3d8129cc939d4e |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-06f7ba557e5e4926ba3d8129cc939d4e2025-01-09T05:10:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15052391505239Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progressionStefano Ruberto0Stefano Ruberto1María I. Domınguez-Mozo2M. Angel Garcıa-Martınez3Davide Cossu4Davide Cossu5Leonardo A. Sechi6Leonardo A. Sechi7Roberto Alvarez-Lafuente8Division of Microbiology and Virology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyEnvironmental Factors in Degenerative Diseases Research Group. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, SpainDivision of Microbiology and Virology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalyDepartment of Neurology, Juntendo University, Tokyo, JapanDivision of Microbiology and Virology, Department of Biomedical Sciences, University of Sassari, Sassari, ItalySC Microbiologia e Virologia, Azienda Ospedaliera Universitaria, Sassari, ItalyEnvironmental Factors in Degenerative Diseases Research Group. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, SpainIntroductionThe envelope proteins syncytin-1 and pHERV-W from the Human Endogenous Retroviral family ‘W’ (HERV-W) have been identified as potential risk factors in multiple sclerosis (MS). This study aims to evaluate both humoral and cell-mediated immune response to antigenic peptides derived from these proteins across different clinical forms and inflammatory phases of MS.MethodsIndirect enzyme-linked immunosorbent assay (ELISA) was employed to measure immunoglobulin G (IgG) responses to syncytin-1env 486-500 and pHERV-Wenv 486-504 peptides in MS patients. Discriminant analysis was used to assess whether clinical course prediction could be enhanced by integrating clinical variables with humoral response data against other MS-associated viral factors. Additionally, peripheral blood mononuclear cells from MS patients and healthy controls (HC) were analyzed for inflammatory responses following stimulation with these peptides.ResultsMS patients exhibited significantly elevated antibody titers against -pHERV-Wenv 486-504 and syncytin-1env 486-500 compared to HCs, with the highest levels observed in progressive MS forms. Discriminant analysis accurately predicted the clinical course in 75.3% of the cases, with an 85% accuracy rate for progressive MS. In vitro, stimulation with pHERV-Wenv 486-504 led to a notable increase in pro-inflammatory cytokine production by CD4, CD8, and CD19 cells compared to syncytin-1env 486-500. A strong correlation was found between pHERV- Wenv 486-504 induced cytokine production and EBV and CMV titers in MS patients.DiscussionThese findings suggest that the pHERV-W envelope protein could be a valuable biomarker for monitoring peripheral inflammation in MS.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505239/fullmultiple sclerosisHERV-Wsyncytin-1biomarkersimmune response |
| spellingShingle | Stefano Ruberto Stefano Ruberto María I. Domınguez-Mozo M. Angel Garcıa-Martınez Davide Cossu Davide Cossu Leonardo A. Sechi Leonardo A. Sechi Roberto Alvarez-Lafuente Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression Frontiers in Immunology multiple sclerosis HERV-W syncytin-1 biomarkers immune response |
| title | Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression |
| title_full | Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression |
| title_fullStr | Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression |
| title_full_unstemmed | Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression |
| title_short | Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression |
| title_sort | immune response profiling of herv w envelope proteins in multiple sclerosis potential biomarkers for disease progression |
| topic | multiple sclerosis HERV-W syncytin-1 biomarkers immune response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505239/full |
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