[Antibodies to glutamate receptor in limbic encephalitis].
N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR), is an important molecule, which contributes to the pathophysiological processes of various neurological diseases by various molecular mechanisms. Antibodies against NMDA-type GluR (NR) are detected by immunoblot analysis, enzyme-linked immunosorbent assay (ELISA), or immunocytochemical analysis (Dalmau's method). Immunoblot method uses whole molecules of GluRepsilon2 (NR2B), which are synthesized in NIH3T3 cells by using tetracycline system as antigens. In ELISA, synthesized peptides of each domain of GluRepsilon2 and GluRtheta1 (NR1) are used. Immunocytochemical method uses human embryonic kidney (HEK) cells transfected by expression vectors for NR1+NR2B/2A. In non-paraneoplastic, non-herpetic acute limbic encephalitis (NHALE), serum antibodies to GluRepsilon2 (NR2B) were detected in approximately 60% of the patients from acute to chronic stages further, these antibodies in the cerebrospinal fluid (CSF) were detected in 50% (acute stage), 40% (recovery stage), and 30% (chronic stage) of the patients. The antibodies against GluRepsilon2 seemed to increase in the sera after infection and infiltrate the central nervous system through the blood-brain barrier (BBB), which was damaged by cytokines, etc. The antibodies against GluRepsilon2 recognize broad regions of GluRepsilon2 as epitopes. In NHALE patients with ovarian teratoma, antibodies to NR recognize epitopes on GluRepsilon2 (NR2B) and GluRtheta1 (NR1). Pathophysiology of antibodies against NR is estimated to cause internalization of NR on surface of neurons, resulting in inhibition of NR function.
Takahashi
Yukitoshi
Y
National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Aoi-ku, Shizuoka, Japan.
Mogami
Yukiko
Y
Takayama
Rumiko
R
Ikeda
Hiroko
H
Imai
Katsumi
K
D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier; D005260:Female; D006801:Humans; D020363:Limbic Encephalitis / Q000276:immunology*; D008297:Male; D009698:Nucleoproteins; D010051:Ovarian Neoplasms; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D013724:Teratoma
D001323:Autoantibodies; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D009698:Nucleoproteins; D016194:Receptors, N-Methyl-D-Aspartate; C090319:peptide 31D