Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_4147F114C817
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate.
Journal
Neurology
Author(s)
Mathias A., Perriot S., Canales M., Blatti C., Gaubicher C., Schluep M., Engelhardt B., Du Pasquier R.
ISSN
2332-7812 (Print)
ISSN-L
2332-7812
Publication state
Published
Issued date
11/2017
Peer-reviewed
Oui
Volume
4
Number
6
Pages
e401
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile.
We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7) was assessed using flow cytometry on CD4(+) and CD8(+) T cells. The adhesion profiles of CD3(+) T cells to specific integrin ligands (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and mucosal vascular addressin cell adhesion molecule-1 [MAdCAM-1]) were measured in vitro before and after 12 and 36-48 months.
NTZ decreased the frequency of α4β1(+) and α4β7(+) integrin expressing T cells and the binding of these cells to VCAM-1 and MAdCAM-1, respectively. After 12 months, DMF induced a decreased frequency of αL(high)CD4(+) T cells combined with reduced binding to ICAM-1. By contrast, with FTY, there was a doubling of the frequency of α4β1(+) and αL(high), but a decreased frequency of α4β7(+) T cells. Strikingly, the binding of α4β1(+), α4β7(+), and to a lesser extent of αL(high) T cells to VCAM-1, MAdCAM-1, and ICAM-1, respectively, was decreased at month 12 under FTY treatment. The presence of manganese partially restored the binding of these T cells to VCAM-1 in vitro, suggesting that FTY interferes with integrin activation.
In addition to NTZ, DMF and FTY but not other tested DMTs may also decrease T-cell-mediated immune surveillance of the CNS. Whether this mechanism may contribute to the onset of CNS opportunistic infections remains to be shown.

Pubmed
Open Access
Yes
Create date
09/11/2017 19:53
Last modification date
20/08/2019 14:41
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