Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab
Granell-Geli, Júlia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Izquierdo-Gracia, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sellés-Rius, Ares (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Teniente Serra, Aina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Presas-Rodríguez, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Mansilla Lopez, Maria Jose (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Brieva Ruiz, Luis (Hospital Universitari Arnau de Vilanova)
Sotoca Fernández, Javier (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Mañé-Martínez, María Alba (Hospital Universitari Joan XXIII de Tarragona)
Moral, Ester (Hospital de Sant Joan Despí Moisès Broggi)
Bragado, Irene (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Goelz, Susan (Biogen Idec)
Martínez Cáceres, Eva María (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ramo-Tello, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	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.
Derechos:	Aquest 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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Biomarker ; CD49d ; Extended interval dose ; Immunomonitoring ; Multiple sclerosis ; Natalizumab ; Personalized dose ; SVCAM-1
Publicado en:	Journal of personalized medicine, Vol. 11 (december 2021) , ISSN 2075-4426

DOI: 10.3390/jpm11121347
PMID: 34945819

19 p, 7.5 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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