Assessing Blood-Based Biomarkers to Define a Therapeutic Window for Natalizumab.

Autor:	Granell-Geli J; Division of Immunology, LCMN Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, 08916 Badalona, Spain.; Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Izquierdo-Gracia C; Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain., Sellés-Rius A; Division of Immunology, LCMN Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, 08916 Badalona, Spain., Teniente-Serra A; Division of Immunology, LCMN Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, 08916 Badalona, Spain.; Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Presas-Rodríguez S; Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain., Mansilla MJ; Division of Immunology, LCMN Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, 08916 Badalona, Spain.; Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Brieva L; Multiple Sclerosis Unit, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain., Sotoca J; Neurology Service, Hospital Universitari Mútua Terrassa, 08221 Terrassa, Spain., Mañé-Martínez MA; Neurology Service, Hospital Universitari Joan XXIII, Universitat Rovira i Virgili, 43005 Tarragona, Spain., Moral E; Multiple Sclerosis Unit, Hospital Sant Joan Despí Moisès Broggi, 08970 Sant Joan Despí, Spain., Bragado I; Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain., Goelz S; Biogen Idec, Cambridge, MA 02142, USA., Martínez-Cáceres E; Division of Immunology, LCMN Hospital Universitari Germans Trias i Pujol and Research Institute, Campus Can Ruti, 08916 Badalona, Spain.; Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Ramo-Tello C; Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain.
Jazyk:	angličtina
Zdroj:	Journal of personalized medicine [J Pers Med] 2021 Dec 10; Vol. 11 (12). Date of Electronic Publication: 2021 Dec 10.
DOI:	10.3390/jpm11121347
Abstrakt:	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/4wks or extended interval dose (EID) of 300 mg/6wks. 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.
Databáze:	MEDLINE
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