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Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells

BACKGROUND: The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4(+) T cells low expression and progressive multifocal leukoenceph...

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Autores principales: Spadaro, Michela, Caldano, Marzia, Marnetto, Fabiana, Lugaresi, Alessandra, Bertolotto, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532246/
https://www.ncbi.nlm.nih.gov/pubmed/26259673
http://dx.doi.org/10.1186/s12974-015-0365-x
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author Spadaro, Michela
Caldano, Marzia
Marnetto, Fabiana
Lugaresi, Alessandra
Bertolotto, Antonio
author_facet Spadaro, Michela
Caldano, Marzia
Marnetto, Fabiana
Lugaresi, Alessandra
Bertolotto, Antonio
author_sort Spadaro, Michela
collection PubMed
description BACKGROUND: The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4(+) T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ. METHODS: We performed a flow cytometric analysis on peripheral blood mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory syndrome) patients and four longitudinal samples of a NTZ-treated patients before and during the development of a clinical asymptomatic magnetic resonance imaging (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. Thirty-five NTZ-treated patients were studied longitudinally with three samples taken 4 months apart. RESULTS: The NTZ-treated patients showed a lower percentage of CD62L (33.68 %, n = 113) than first-line treated patients (44.24 %, n = 52, p = 0.0004). NTZ effect was already clear during the first year of treatment (34.68 %; p = 0.0184); it persisted in the following years and disappeared after drug withdrawal (44.08 %). Three percent of longitudinally analysed patients showed a percentage of CD62LCD4(+) T cells under a hypothetical threshold and one patient with asymptomatic PML belongs to a group which expressed low percentage of CD62LCD4(+) T cells. CONCLUSIONS: Our research confirms that NTZ has a specific effect on CD62LCD4(+) T cells consisting in decreasing of the number of positive cells. The low level of CD62L found in a clinically asymptomatic PML patient strengthens its potential usefulness as a biomarker of high PML risk in NTZ-treated patients. A larger study is required to better confirm the data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0365-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-45322462015-08-12 Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells Spadaro, Michela Caldano, Marzia Marnetto, Fabiana Lugaresi, Alessandra Bertolotto, Antonio J Neuroinflammation Research BACKGROUND: The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4(+) T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ. METHODS: We performed a flow cytometric analysis on peripheral blood mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory syndrome) patients and four longitudinal samples of a NTZ-treated patients before and during the development of a clinical asymptomatic magnetic resonance imaging (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. Thirty-five NTZ-treated patients were studied longitudinally with three samples taken 4 months apart. RESULTS: The NTZ-treated patients showed a lower percentage of CD62L (33.68 %, n = 113) than first-line treated patients (44.24 %, n = 52, p = 0.0004). NTZ effect was already clear during the first year of treatment (34.68 %; p = 0.0184); it persisted in the following years and disappeared after drug withdrawal (44.08 %). Three percent of longitudinally analysed patients showed a percentage of CD62LCD4(+) T cells under a hypothetical threshold and one patient with asymptomatic PML belongs to a group which expressed low percentage of CD62LCD4(+) T cells. CONCLUSIONS: Our research confirms that NTZ has a specific effect on CD62LCD4(+) T cells consisting in decreasing of the number of positive cells. The low level of CD62L found in a clinically asymptomatic PML patient strengthens its potential usefulness as a biomarker of high PML risk in NTZ-treated patients. A larger study is required to better confirm the data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0365-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-12 /pmc/articles/PMC4532246/ /pubmed/26259673 http://dx.doi.org/10.1186/s12974-015-0365-x Text en © Spadaro et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Spadaro, Michela
Caldano, Marzia
Marnetto, Fabiana
Lugaresi, Alessandra
Bertolotto, Antonio
Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells
title Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells
title_full Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells
title_fullStr Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells
title_full_unstemmed Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells
title_short Natalizumab treatment reduces L-selectin (CD62L) in CD4(+) T cells
title_sort natalizumab treatment reduces l-selectin (cd62l) in cd4(+) t cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532246/
https://www.ncbi.nlm.nih.gov/pubmed/26259673
http://dx.doi.org/10.1186/s12974-015-0365-x
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