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Antibodies to the Glutamate Receptor Yukitoshi Takahashi 1,2 , Mamiko Hotate 1 , Yuki Ueda 1 , Tokito Yamaguchi 1 , Hirosato Nasu 1 1National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders 2Department of Pediatrics, Gifu University School of Medicine Keyword: NMDA-type glutamate receptor , GluRε2 (GluN2B and NR2B) , GluRζ1 (GluN1 and NR1) , acute limbic encephalitis , ovarian teratoma pp.345-353
Published Date 2013/4/1
DOI https://doi.org/10.11477/mf.1416101459
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Abstract

 Glutamate receptors (GluRs) are classified into metabotropic GluRs and ionotropic GluRs. Ionotropic GluRs include the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) -type, kainate (KA)-type, and N-methyl-D-aspartate (NMDA)-type GluRs (NRs).

 Antibodies to the NRs have been detected using immunoblot, cell-based assays, and enzyme linked immunosorbent assay (ELISA). In patient with non-paraneoplastic, non-herpetic acute limbic encephalitis (NHALE), antibodies against GluN2B (GluRε2) and GluN1 (Gluζ1) are detected in the sera and CSF. In addition to the antibodies to NRs detected by ELISA, antibodies to an NR-complex detected by cell-based assay are found, not only in CSF from NHALE, but also in CSF from epilepsy, Creutzfeldt-Jakob disease (CJD), etc. Antibodies to NRs internalize mainly extra-synaptic NRs, and dissociate the connection between GluN2A and Ephrin-B2 receptor at the synapse. IgG fractions containing antibodies to NRs decrease apoptosis of cultured neurons.

 Antibodies to AMPA-type GluRs have been detected by immunoblot, cell-based assay and ELISA. In Rasmussen syndrome, antibodies against GluA3 (GluR3) were found to be the primary pathological factor. However the antibodies did not cause Rasmussen syndrome in mice models. These antibodies have been shown to cause excitotoxicity through GluA3, complement-dependent cytotoxicity, etc. Antibodies to GluA1/GluA2 in paraneoplastic limbic encephalitis modulate expression and localization of GluA1/GluA2 at the synapse.

 Antibodies to metabotropic GluRs have been detected using cell-based assays in patients with Hodgkin's lymphoma. Passive transfer of the IgG fraction from patients having antibodies to metabotropic GluR1 causes ataxia in mice.


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電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院

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