[PS2-1B-3] Roles of antibodies to NMDA-type glutamate receptors in altered behavior & cognition of patients with epileptic encephalopathy
[Introduction]
Patients with epileptic encephalopathy show mental retardation by cognitive dysfunction and autistic behaviour, evolutionally. The pathophysiology of epileptic encephalopathy has not been fully understood. We want to reveal the pathophysiological mechanisms from the point of neuroimmunology.
[Antibodies to NMDA-type GluRs in West syndrome]
CSF samples were collected from 33 patients with epileptic spasms. The CSF levels of antibodies against peptides of NMDA-type GluR subunits (GluN2B & GluN1) were measured by ELISA. The levels of antibodies against the n-terminal of GluN2B (GluN2B-NT2), c-terminal of GluN2B and n-terminal of GluN1, were significantly higher in patients. Levels of antibodies to GluN2B showed evidence of correlation with intervals from the onset to the examination of CSF until 25 months. The correlation was significant in patients with unknown cause. Five of 33 patients with higher level of antibodies to GluN2B had poor motor and cognitive outcomes.
[Passive transfer of antibodies to GluN2B-NT2]
Rabbits were immunized by human GluN2B-NT2 peptide, and their sera were purified into polyclonal antibodies to GluN2B-NT2. The antibodies to GluN2B-NT2 were introduced into hippocampi of mice. Straub tail reaction in mice of antibodies to GluN2B-NT2 group was increased significantly at 7th day. Light / dark chamber tests showed that spent time in light chambers was significantly higher in antibodies to GluN2B-NT2 group. Social interaction tests suggested that counts of active social interaction were significantly lower in antibodies to GluN2B-NT2 group.
[Conclusions]
Antibodies to NMDA-type GluRs may be causally related with altered behavior and cognition of patients with epileptic encephalopathy.
Patients with epileptic encephalopathy show mental retardation by cognitive dysfunction and autistic behaviour, evolutionally. The pathophysiology of epileptic encephalopathy has not been fully understood. We want to reveal the pathophysiological mechanisms from the point of neuroimmunology.
[Antibodies to NMDA-type GluRs in West syndrome]
CSF samples were collected from 33 patients with epileptic spasms. The CSF levels of antibodies against peptides of NMDA-type GluR subunits (GluN2B & GluN1) were measured by ELISA. The levels of antibodies against the n-terminal of GluN2B (GluN2B-NT2), c-terminal of GluN2B and n-terminal of GluN1, were significantly higher in patients. Levels of antibodies to GluN2B showed evidence of correlation with intervals from the onset to the examination of CSF until 25 months. The correlation was significant in patients with unknown cause. Five of 33 patients with higher level of antibodies to GluN2B had poor motor and cognitive outcomes.
[Passive transfer of antibodies to GluN2B-NT2]
Rabbits were immunized by human GluN2B-NT2 peptide, and their sera were purified into polyclonal antibodies to GluN2B-NT2. The antibodies to GluN2B-NT2 were introduced into hippocampi of mice. Straub tail reaction in mice of antibodies to GluN2B-NT2 group was increased significantly at 7th day. Light / dark chamber tests showed that spent time in light chambers was significantly higher in antibodies to GluN2B-NT2 group. Social interaction tests suggested that counts of active social interaction were significantly lower in antibodies to GluN2B-NT2 group.
[Conclusions]
Antibodies to NMDA-type GluRs may be causally related with altered behavior and cognition of patients with epileptic encephalopathy.