Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab
Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:282871 |
| Acesso em linha: | https://ddd.uab.cat/record/282871 https://dx.doi.org/urn:doi:10.3390/jpm11121347 |
| Access Level: | acceso abierto |
| Palavra-chave: | Biomarker CD49d Extended interval dose Immunomonitoring Multiple sclerosis Natalizumab Personalized dose SVCAM-1 |
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Assessing Blood-Based Biomarkers to Define a Therapeutic Window for NatalizumabGranell-Geli, Júlia|||0000-0002-3369-9765Izquierdo, CristinaSellés-Rius, Ares|||0000-0002-9745-7749Teniente Serra, Aina|||0000-0003-3440-804XPresas Rodríguez, Sílvia|||0000-0001-8545-2476Mansilla Lopez, Maria Jose|||0000-0002-5044-6313Brieva Ruiz, Luis|||0000-0002-5871-6189Sotoca Fernández, Javier|||0000-0003-3400-1434Mañé-Martínez, María AlbaMoral, EsterBragado, IreneGoelz, SusanMartínez Cáceres, Eva María|||0000-0002-6762-8025Ramo-Tello, Cristina|||0000-0001-8643-5053BiomarkerCD49dExtended interval doseImmunomonitoringMultiple sclerosisNatalizumabPersonalized doseSVCAM-1Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4 wks or extended interval dose (EID) of 300 mg/6 wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual's dosing schedule.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/282871https://dx.doi.org/urn:doi:10.3390/jpm11121347reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2828712026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| title |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| spellingShingle |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab Granell-Geli, Júlia|||0000-0002-3369-9765 Biomarker CD49d Extended interval dose Immunomonitoring Multiple sclerosis Natalizumab Personalized dose SVCAM-1 |
| title_short |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| title_full |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| title_fullStr |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| title_full_unstemmed |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| title_sort |
Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab |
| dc.creator.none.fl_str_mv |
Granell-Geli, Júlia|||0000-0002-3369-9765 Izquierdo, Cristina Sellés-Rius, Ares|||0000-0002-9745-7749 Teniente Serra, Aina|||0000-0003-3440-804X Presas Rodríguez, Sílvia|||0000-0001-8545-2476 Mansilla Lopez, Maria Jose|||0000-0002-5044-6313 Brieva Ruiz, Luis|||0000-0002-5871-6189 Sotoca Fernández, Javier|||0000-0003-3400-1434 Mañé-Martínez, María Alba Moral, Ester Bragado, Irene Goelz, Susan Martínez Cáceres, Eva María|||0000-0002-6762-8025 Ramo-Tello, Cristina|||0000-0001-8643-5053 |
| author |
Granell-Geli, Júlia|||0000-0002-3369-9765 |
| author_facet |
Granell-Geli, Júlia|||0000-0002-3369-9765 Izquierdo, Cristina Sellés-Rius, Ares|||0000-0002-9745-7749 Teniente Serra, Aina|||0000-0003-3440-804X Presas Rodríguez, Sílvia|||0000-0001-8545-2476 Mansilla Lopez, Maria Jose|||0000-0002-5044-6313 Brieva Ruiz, Luis|||0000-0002-5871-6189 Sotoca Fernández, Javier|||0000-0003-3400-1434 Mañé-Martínez, María Alba Moral, Ester Bragado, Irene Goelz, Susan Martínez Cáceres, Eva María|||0000-0002-6762-8025 Ramo-Tello, Cristina|||0000-0001-8643-5053 |
| author_role |
author |
| author2 |
Izquierdo, Cristina Sellés-Rius, Ares|||0000-0002-9745-7749 Teniente Serra, Aina|||0000-0003-3440-804X Presas Rodríguez, Sílvia|||0000-0001-8545-2476 Mansilla Lopez, Maria Jose|||0000-0002-5044-6313 Brieva Ruiz, Luis|||0000-0002-5871-6189 Sotoca Fernández, Javier|||0000-0003-3400-1434 Mañé-Martínez, María Alba Moral, Ester Bragado, Irene Goelz, Susan Martínez Cáceres, Eva María|||0000-0002-6762-8025 Ramo-Tello, Cristina|||0000-0001-8643-5053 |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Biomarker CD49d Extended interval dose Immunomonitoring Multiple sclerosis Natalizumab Personalized dose SVCAM-1 |
| topic |
Biomarker CD49d Extended interval dose Immunomonitoring Multiple sclerosis Natalizumab Personalized dose SVCAM-1 |
| description |
Natalizumab is a monoclonal antibody that binds CD49d. Although it is one of the most effective treatments for Relapsing-Remitting Multiple Sclerosis (RRMS), a dosing regimen has not been optimized for safety and efficacy in individual patients. We aimed to identify biomarkers to monitor Natalizumab treatment and to establish a personalized dose utilizing an ongoing longitudinal study in 29 RRMS patients under Natalizumab with standard interval dose (SD) of 300 mg/4 wks or extended interval dose (EID) of 300 mg/6 wks. Blood samples were analyzed by flow cytometry to determine CD49d saturation and expression in several T and B lymphocytes subpopulations. Each patient was analyzed at two different timepoints separated by 3 Natalizumab administrations. Natalizumab and sVCAM-1 levels in serum were also analyzed using ELISA. To determine the reproducibility of various markers, two different timepoints were compared and no significant differences were observed for CD49d expression nor for saturation; SD patients had higher saturation levels (~80%) than EID patients (~60%). A positive correlation exists between CD49d saturation and Natalizumab serum levels. CD49d expression and saturation are stable parameters that could be used as biomarkers in the immunomonitoring of Natalizumab treatment. Moreover, Natalizumab and sVCAM-1 serum levels could be used to optimize an individual's dosing schedule. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2 2021-01-01 2021 2021-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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https://ddd.uab.cat/record/282871 https://dx.doi.org/urn:doi:10.3390/jpm11121347 |
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https://ddd.uab.cat/record/282871 https://dx.doi.org/urn:doi:10.3390/jpm11121347 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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