Highlights
- •Immune responses in the central nervous system (CNS) are highly compartmentalized.
- •pDCs were maintained in CSF but depleted from blood by alemtuzumab.
- •Genes associated with migration were elevated only in the CSF after alemtuzumab.
- •The CSF and blood compartments are thus partially uncoupled.
Abstract
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.
Keywords
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Article info
Publication history
Published online: April 11, 2023
Accepted:
April 8,
2023
Received in revised form:
April 3,
2023
Received:
February 21,
2023
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
