Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
03
05
2021
received:
14
01
2021
accepted:
03
05
2021
pubmed:
6
5
2021
medline:
15
9
2021
entrez:
5
5
2021
Statut:
ppublish
Résumé
The objective of this study was to report the identification of antibodies against the glutamate kainate receptor subunit 2 (GluK2-abs) in patients with autoimmune encephalitis, and describe the clinical-immunological features and antibody effects. Two sera from 8 patients with similar rat brain immunostaining were used to precipitate the antigen from neuronal cultures. A cell-based assay (CBA) with GluK2-expressing HEK293 cells was used to assess 596 patients with different neurological disorders, and 23 healthy controls. GluK2-ab effects were determined by confocal microscopy in cultured neurons and electrophysiology in GluK2-expressing HEK293 cells. Patients' antibodies precipitated GluK2. GluK2 antibody-specificity was confirmed by CBA, immunoprecipitation, GluK2-immunoabsorption, and GluK2 knockout brain immunohistochemistry. In 2 of 8 samples, antibodies reacted with additional GluK2 epitopes present in GluK1 or GluK3; in both, the reactivity was abrogated after GluK2 immuno-absorption. Six of 8 patients developed acute encephalitis and clinical or magnetic resonance imaging (MRI) features of predominant cerebellar involvement (4 presenting as cerebellitis, which in 2 patients caused obstructive hydrocephalus), and 2 patients had other syndromes (1 with cerebellar symptoms). One of the samples showed mild reactivity with non-kainate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPAR] and N-methyl-D-aspartate receptors [NMDAR]) leading to identify 6 additional cases with GluK2-abs among patients with anti-AMPAR (5/71) or anti-NMDAR encephalitis (1/73). GluK2-abs internalized GluK2 in HEK293 cells and neurons; these antibody-effects were reversible in neurons. A significant reduction of GluK2-mediated currents was observed in cells treated with patients' GluK2 serum following the time frame of antibody-mediated GluK2 internalization. GluK2-abs associate with an encephalitis with prominent clinicoradiological cerebellar involvement. The antibody effects are predominantly mediated by internalization of GluK2. ANN NEUROL 2021;90:107-123.
Substances chimiques
Autoantibodies
0
Receptors, Kainic Acid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101-117Subventions
Organisme : "la Caixa" Foundation
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 2019FI_B100212
Organisme : Basque Government Doctoral Fellowship Programme
ID : PRE_2019_1_0255
Organisme : CIBERER CB15/00010
Organisme : Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
ID : 2017SGR737
Organisme : Edmond J. Safra Center foundation
Organisme : ERA-NET NEURON
Organisme : European Regional Development Fund
ID : BFU2017-83317-P
Organisme : Fundació Cellex
Organisme : Instituto de Salud Carlos III
ID : JR17/00012
Organisme : Instituto de Salud Carlos III
ID : PI20/00197
Organisme : Instituto de Salud Carlos III
ID : PI17/00296
Organisme : Instituto de Salud Carlos III
ID : PI18/00067
Organisme : Instituto de Salud Carlos III
ID : PI18/00486
Organisme : Instituto de Salud Carlos III
ID : Proyecto Integrado de Excelencia 16/00014
Organisme : Instituto de Salud Carlos III
ID : RD16/0008/0014
Organisme : Ministerio de Ciencia e Innovación
ID : Maria de Maeztu MDM-2017-0729
Organisme : Pablove Foundation
ID : 689368
Organisme : Pla estratègic de recerca i innovació en salut (PERIS)
ID : SLT006/17/00362
Organisme : Resident Award Josep Font, Hospital Clinic de Barcelona
Organisme : Torrons Vicenç foundation
ID : PFNR0144
Informations de copyright
© 2021 American Neurological Association.
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