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Journal of Neuroinflammation

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Open Access 01-12-2015 | Research

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

Authors: Michela Spadaro, Marzia Caldano, Fabiana Marnetto, Alessandra Lugaresi, Antonio Bertolotto

Published in: Journal of Neuroinflammation | Issue 1/2015

Abstract

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.

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Title: Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells
Authors: Michela Spadaro
Marzia Caldano
Fabiana Marnetto
Alessandra Lugaresi
Antonio Bertolotto
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-015-0365-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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