Subcutaneous anti-CD20 antibody treatment delays gray matter atrophy in human myelin oligodendrocyte glycoprotein-induced EAE mice.
Animals
Antibodies
/ therapeutic use
Antigens, CD20
/ immunology
Atrophy
B-Lymphocytes
/ immunology
Brain
/ diagnostic imaging
Demyelinating Diseases
/ chemically induced
Encephalomyelitis, Autoimmune, Experimental
/ chemically induced
Female
Gray Matter
/ diagnostic imaging
Humans
Macrophages
/ immunology
Magnetic Resonance Imaging
Mice
Mice, Inbred C57BL
Myelin-Oligodendrocyte Glycoprotein
/ immunology
Postural Balance
/ drug effects
Psychomotor Performance
/ drug effects
Anti-CD20 antibody
Brain atrophy
Gray matter atrophy
Histology
MRI
Multiple sclerosis
huMOG-EAE
Journal
Experimental neurology
ISSN: 1090-2430
Titre abrégé: Exp Neurol
Pays: United States
ID NLM: 0370712
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
21
07
2020
revised:
18
09
2020
accepted:
25
09
2020
pubmed:
30
9
2020
medline:
20
4
2021
entrez:
29
9
2020
Statut:
ppublish
Résumé
The human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (huMOG-EAE) model, generates B-cell driven demyelination in mice, making it a suitable multiple sclerosis model to study B cell depletion. We investigated the effect of subcutaneous anti-CD20 antibody treatment on huMOG-EAE gray matter (GM) pathology. C57Bl/6, 8-week old mice were immunized with 200 huMOG Anti-CD20 antibody significantly reduced brain volume loss compared with the isotype control across all timepoints longitudinally in the basal ganglia (p = 0.01), isocortex (p = 0.025) and thalamus (p = 0.023). The CDS was reduced significantly with anti-CD20 antibody vs. the isotype control at 3 (p = 0.003) and 4 (p = 0.03) wkPI, while a trend was observed at 5 (p = 0.057) and 6 (p = 0.086) wkPI. Performance on rotarod was also improved significantly at 3 (p = 0.007) and 5 (p = 0.01) wkPI compared with the isotype control. At cellular level, anti-CD20 therapy suppressed the percentage of proliferative nuclear antigen positive microglia in huMOG-EAE isocortex (p = 0.016). Flow cytometry confirmed that anti-CD20 antibody strongly depleted the CD19-expressing B cell fraction in peripheral blood mononuclear cells, reducing it from 39.7% measured in isotype control to 1.59% in anti-CD20 treated mice (p < 0.001). Anti-CD20 antibody treatment delayed brain tissue neurodegeneration in GM, and showed clinical benefit on measures of disease severity in huMOG-EAE mice.
Sections du résumé
BACKGROUND
The human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (huMOG-EAE) model, generates B-cell driven demyelination in mice, making it a suitable multiple sclerosis model to study B cell depletion.
OBJECTIVES
We investigated the effect of subcutaneous anti-CD20 antibody treatment on huMOG-EAE gray matter (GM) pathology.
METHODS
C57Bl/6, 8-week old mice were immunized with 200 huMOG
RESULTS
Anti-CD20 antibody significantly reduced brain volume loss compared with the isotype control across all timepoints longitudinally in the basal ganglia (p = 0.01), isocortex (p = 0.025) and thalamus (p = 0.023). The CDS was reduced significantly with anti-CD20 antibody vs. the isotype control at 3 (p = 0.003) and 4 (p = 0.03) wkPI, while a trend was observed at 5 (p = 0.057) and 6 (p = 0.086) wkPI. Performance on rotarod was also improved significantly at 3 (p = 0.007) and 5 (p = 0.01) wkPI compared with the isotype control. At cellular level, anti-CD20 therapy suppressed the percentage of proliferative nuclear antigen positive microglia in huMOG-EAE isocortex (p = 0.016). Flow cytometry confirmed that anti-CD20 antibody strongly depleted the CD19-expressing B cell fraction in peripheral blood mononuclear cells, reducing it from 39.7% measured in isotype control to 1.59% in anti-CD20 treated mice (p < 0.001).
CONCLUSIONS
Anti-CD20 antibody treatment delayed brain tissue neurodegeneration in GM, and showed clinical benefit on measures of disease severity in huMOG-EAE mice.
Identifiants
pubmed: 32991933
pii: S0014-4886(20)30319-8
doi: 10.1016/j.expneurol.2020.113488
pii:
doi:
Substances chimiques
Antibodies
0
Antigens, CD20
0
MOG protein, human
0
Myelin-Oligodendrocyte Glycoprotein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113488Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.