Naslov
Encephalitis with autoantibodies against the glutamate kainate receptors GluK2

Autori
Landa, Jon ; Guasp, Mar ; Míguez-Cabello, Federico ; Guimarães, Joana ; Mishima, Takayasu ; Oda, Fumiko ; Zipp, Frauke ; Krajinović, Vladimir ; Fuhr, Peter ; Honnorat, Jerome ; Titulaer, Maarteen ; Simabukuro, Mateus ; Planagumà, Jesus ; Martínez-Hernández, Eugenia ; Armangué, Thais ; Saiz, Albert ; Gasull, Xavier ; Soto, David ; Graus, Francesc ; Sabater, Lidia ; Dalmau, Joseph ;

Kolaboracija
GluK2 encephalitis study group

Izvornik
Annals of neurology (0364-5134) 90 (2021), 1; 101-117

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
encephalitis ; autoantibodies ; GluK2

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Integrativna bioetika (prirodne, tehničke, biomedicina i zdravstvo, biotehničke, društvene, humanističke znanosti)

POVEZANOST RADA