Alemtuzumab treatment exemplifies discordant immune effects of blood and cerebrospinal fluid in multiple sclerosis.
Alemtuzumab
Multiple sclerosis
Single cell RNA sequencing
Journal
Journal of neuroimmunology
ISSN: 1872-8421
Titre abrégé: J Neuroimmunol
Pays: Netherlands
ID NLM: 8109498
Informations de publication
Date de publication:
15 05 2023
15 05 2023
Historique:
received:
21
02
2023
revised:
03
04
2023
accepted:
08
04
2023
medline:
8
5
2023
pubmed:
17
4
2023
entrez:
16
4
2023
Statut:
ppublish
Résumé
Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans. We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing. As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab. The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood.
Sections du résumé
BACKGROUND AND OBJECTIVES
Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans.
METHODS
We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing.
RESULTS
As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab.
DISCUSSION
The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood.
Identifiants
pubmed: 37062182
pii: S0165-5728(23)00074-7
doi: 10.1016/j.jneuroim.2023.578088
pii:
doi:
Substances chimiques
Alemtuzumab
3A189DH42V
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
578088Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest GMzH received compensation for serving on scientific advisory boards (LFB) and speaker honoraria (Alexion). HW is acting as a paid consultant for AbbVie, Actelion, Biogen, IGES, Johnson & Johnson, Novartis, Roche, Sanofi-Aventis, and the Swiss Multiple Sclerosis Society. The remaining authors declare no financial interests or conflicts of interest.