PMID- 32893288
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210216
IS  - 1460-2156 (Electronic)
IS  - 0006-8950 (Linking)
VI  - 143
IP  - 10
DP  - 2020 Oct 1
TI  - Autoimmune encephalitis mediated by B-cell response against N-methyl-d-aspartate 
      receptor.
PG  - 2957-2972
LID - 10.1093/brain/awaa250 [doi]
AB  - Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a neuropsychiatric 
      disease characterized by an antibody-mediated autoimmune response against NMDAR. 
      Recent studies have shown that anti-NMDAR antibodies are involved in the 
      pathophysiology of the disease. However, the upstream immune and inflammatory 
      processes responsible for this pathogenic response are still poorly understood. 
      Here, we immunized mice against the region of NMDA receptor containing the 
      N368/G369 amino acids, previously implicated in a pathogenic response. This 
      paradigm induced encephalopathy characterized by blood-brain barrier opening, 
      periventricular T2-MRI hyperintensities and IgG deposits into the brain 
      parenchyma. Two weeks after immunization, mice developed clinical symptoms 
      reminiscent of encephalitis: anxiety- and depressive-like behaviours, spatial 
      memory impairment (without motor disorders) and increased sensitivity to 
      seizures. This response occurred independently of overt T-cell recruitment. 
      However, it was associated with B220+ (B cell) infiltration towards the 
      ventricles, where they differentiated into CD138+ cells (plasmocytes). 
      Interestingly, these B cells originated from peripheral lymphoid organs (spleen 
      and cervical lymphoid nodes). Finally, blocking the B-cell response using a 
      depleting cocktail of antibodies reduced the severity of symptoms in encephalitis 
      mice. This study demonstrates that the B-cell response can lead to an autoimmune 
      reaction against NMDAR that drives encephalitis-like behavioural impairments. It 
      also provides a relevant platform for dissecting encephalitogenic mechanisms in 
      an animal model, and enables the testing of therapeutic strategies targeting the 
      immune system in anti-NMDAR encephalitis.
CI  - (c) The Author(s) (2020). Published by Oxford University Press on behalf of the 
      Guarantors of Brain. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Wagnon, Isabelle
AU  - Wagnon I
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Helie, Pauline
AU  - Helie P
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Bardou, Isabelle
AU  - Bardou I
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Regnauld, Caroline
AU  - Regnauld C
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Lesec, Leonie
AU  - Lesec L
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Leprince, Jerome
AU  - Leprince J
AD  - Normandie Univ, UNIROUEN, INSERM, U1239, Neuronal and Neuroendocrine 
      Differentiation and Communication, Rouen, France.
FAU - Naveau, Mikael
AU  - Naveau M
AD  - Normandie Univ, UNICAEN, CNRS UMS 3408, Cyceron, Caen, France.
FAU - Delaunay, Barbara
AU  - Delaunay B
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Toutirais, Olivier
AU  - Toutirais O
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
AD  - Department of Immunology, Caen University Hospital, CHU Caen, Caen, France.
FAU - Lemauff, Brigitte
AU  - Lemauff B
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
AD  - Department of Immunology, Caen University Hospital, CHU Caen, Caen, France.
FAU - Etard, Olivier
AU  - Etard O
AD  - Normandie Univ, UNICAEN, ISTS, EA 7466, Cyceron, Caen, France.
AD  - Service des explorations fonctionnelles du systeme nerveux, CHU de Caen, Caen, 
      France.
FAU - Vivien, Denis
AU  - Vivien D
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
AD  - Department of Clinical Research, Caen University Hospital, CHU Caen, Caen, 
      France.
FAU - Agin, Veronique
AU  - Agin V
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Macrez, Richard
AU  - Macrez R
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
AD  - Emergency Department, Caen University Hospital, CHU Caen, Caen France.
FAU - Maubert, Eric
AU  - Maubert E
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
FAU - Docagne, Fabian
AU  - Docagne F
AD  - Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of 
      Neurological Disorders", Institut Blood and Brain at Caen-Normandie, Cyceron, 
      Caen, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Autoantibodies)
RN  - 0 (Gprin1 protein, mouse)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - Hashimoto's encephalitis
SB  - IM
MH  - Animals
MH  - Autoantibodies/*blood/immunology
MH  - B-Lymphocytes/immunology/*metabolism
MH  - Encephalitis/*blood/chemically induced/immunology
MH  - Hashimoto Disease/*blood/chemically induced/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/immunology/*toxicity
MH  - Receptors, N-Methyl-D-Aspartate/immunology
OTO - NOTNLM
OT  - autoimmune encephalitis
OT  - glutamate
OT  - limbic
OT  - neuropsychiatry
OT  - paraneoplastic
EDAT- 2020/09/08 06:00
MHDA- 2021/02/17 06:00
CRDT- 2020/09/07 05:59
PHST- 2019/07/29 00:00 [received]
PHST- 2020/05/06 00:00 [revised]
PHST- 2020/06/29 00:00 [accepted]
PHST- 2020/09/08 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/09/07 05:59 [entrez]
AID - 5902131 [pii]
AID - 10.1093/brain/awaa250 [doi]
PST - ppublish
SO  - Brain. 2020 Oct 1;143(10):2957-2972. doi: 10.1093/brain/awaa250.