Portal de investigação
Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Landa, J
- Guasp, M
- Míguez-Cabello, F
- Mishima, T
- Oda, F
- Zipp, F
- Krajinovic, V
- Fuhr, P
- Honnorat, J
- Titulaer, M
- Simabukuro, M
- Planagumà, J
- Martínez-Hernández, E
- Armangué, T
- Saiz, A
- Gasull, X
- Soto, D
- Graus, F
- Sabater, L
- Dalmau, J
- Gluk2 Encephalitis Study Grp
Unidades de investigação
Abstract
Objective 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. Methods 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. Results 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. Interpretation GluK2-abs associate with an encephalitis with prominent clinicoradiological cerebellar involvement. The antibody effects are predominantly mediated by internalization of GluK2. ANN NEUROL 2021
Dados da publicação
- ISSN/ISSNe:
- 1531-8249, 0364-5134
- Tipo:
- Article
- Páginas:
- 101-117
- DOI:
- 10.1002/ana.26098
- PubMed:
- 33949707
Annals of Neurology John Wiley & Sons Inc.
Citações Recebidas na Web of Science: 12
Documentos
- Não há documentos
Filiações
Keywords
- OPSOCLONUS-MYOCLONUS SYNDROME; CASE SERIES; ACUTE CEREBELLITIS; ANTIBODIES; NMDA; AMPA; TERM; MECHANISMS; PLASTICITY; ANTIGEN
Financiamento
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