Humoral signatures of MOG-antibody-associated disease track with age and disease activity.
Fc gamma receptors
MOGAD
antibody
demyelination
humoral signatures
myelin oligodendrocyte glycoprotein
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
21 02 2023
21 02 2023
Historique:
received:
26
08
2022
revised:
26
10
2022
accepted:
24
12
2022
pubmed:
21
1
2023
medline:
25
2
2023
entrez:
20
1
2023
Statut:
ppublish
Résumé
Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating disease of the CNS. Although MOG is encephalitogenic in different mammalian species, the mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral immune responses in 123 patients with MOGAD. We show that age is a major determinant for MOG-antibody-related immune signatures. Unsupervised clustering additionally identifies two dominant immunological endophenotypes of MOGAD. The pro-inflammatory endophenotype characterized by increased binding affinities for activating Fcγ receptors (FcγRs), capacity to activate innate immune cells, and decreased frequencies of galactosylated and sialylated immunoglobulin G (IgG) glycovariants is associated with clinically active disease. Our data support the concept that FcγR-mediated effector functions control the pathogenicity of MOG-specific IgG and suggest that FcγR-targeting therapies should be explored for their therapeutic potential in MOGAD.
Identifiants
pubmed: 36669487
pii: S2666-3791(22)00492-X
doi: 10.1016/j.xcrm.2022.100913
pmc: PMC9975090
pii:
doi:
Substances chimiques
Receptors, IgG
0
Myelin-Oligodendrocyte Glycoprotein
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100913Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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