[Autoimmune encephalitis-update: roles of autoantibodies in the pathogenesis]

Autoimmune encephalitis is increasingly recognized having autoantibodies to synaptic cell surface antigens, such as anti-N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated protein 1 (LGI1) by neurologists as well as pediatricians and psychiatrists, because these antibodies have been detected in cases of intractable epilepsy or atypical psychosis and in some demyelinating diseases, together with typical limbic encephalitis. Each group have characteristic clinical features, however, the disease spectrum has been expanding. To understand the significance of anti-NMDAR antibodies in the pathogenesis of NMDAR encephalitis, the role of the antibody in the disease process have been evaluated. The binding of antibody is shown to dimerize NMDARs and trigger their internalization on the postsynaptic site, thereby suppressing NMDAR-mediated transmission. To evaluate the antibody-induced dysfunction of NMDARs, we tested and showed the antibodies from the patients suppress the induction of NMDAR-dependent long-term potentiation (LTP) in mouse hippocampal slices. We also tested the antibody-effects on the cognitive functions of mice and revealed the CSF from NMDAR encephalitis patients had effects on disturbing spacial memory in mice. These results firmly support the proposal that the anti-NMDAR encephalitis autoantibody is responsible for cognitive disorders accompanying in this disease.