Novel insights into pathophysiology and therapeutic possibilities reveal further differences between AQP4-IgG- and MOG-IgG-associated diseases.
Journal
Current opinion in neurology
ISSN: 1473-6551
Titre abrégé: Curr Opin Neurol
Pays: England
ID NLM: 9319162
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
pubmed:
19
4
2020
medline:
29
1
2021
entrez:
19
4
2020
Statut:
ppublish
Résumé
This review summarizes recent insights into the pathogenesis and therapeutic options for patients with MOG- or AQP4-antibodies. Although AQP4-IgG are linked to NMOSD, MOG-IgG-associated diseases (MOGAD) include a broader clinical spectrum of autoimmune diseases of the central nervous system (CNS). Details of membrane assembly of AQP4-IgG required for complement activation have been uncovered. Affinity-purified MOG-IgG from patients were shown to be pathogenic by induction of demyelination when the blood--brain barrier (BBB) was breached and by enhancement of activation of cognate T cells. A high-affinity AQP4-IgG, given peripherally, could induce NMOSD-like lesions in rats in the absence of BBB breach. Circulating AQP4-specific and MOG-specific B cells were identified and suggest differences in origin of MOG-antibodies or AQP4-antibodies. Patients with MOG-IgG show a dichotomy concerning circulating MOG-specific B cells; whether this is related to differences in clinical response of anti-CD20 therapy remains to be analyzed. Clinical trials of AQP4-IgG-positive NMOSD patients showed success with eculizumab (preventing cleavage of complement factor C5, thereby blocking formation of chemotactic C5a and membrane attack complex C9neo), inebilizumab (depleting CD19 + B cells), and satralizumab (anti-IL-6R blocking IL-6 actions). New insights into pathological mechanisms and therapeutic responses argue to consider NMOSD with AQP4-IgG and MOGAD as separate disease entities.
Identifiants
pubmed: 32304439
doi: 10.1097/WCO.0000000000000813
pii: 00019052-202006000-00017
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Aquaporin 4
0
Autoantibodies
0
Immunoglobulin G
0
Immunologic Factors
0
Myelin-Oligodendrocyte Glycoprotein
0
inebilizumab
74T7185BMM
eculizumab
A3ULP0F556
satralizumab
YB18NF020M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
362-371Références
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