N-methyl-D-aspartate receptors (NMDARs) are one type of
ionotropic glutamate receptors (GluRs) and are heterotetrametric
cation channels composed of
NMDAR1 (NR1), NMDAR2 (NR2A, 2B, 2C or 2D) and NMDAR3 (NR3A or NR3B) subunits. The main subunits are NR1 and NR2 and their combinations are classified into several diverse forms including NR1/NR1/NR2A/NR2A, NR1/NR1/NR2B/NR2B and NR1/NR1/NR2A/NR2B. NMDARs are physiologically related to synapse development and synaptic plasticity in the central nervous system.
Anti-NMDAR encephalitis is a form of
autoimmune limbic encephalitis mainly affecting young women, with various manifestations including initial psychiatric symptoms, subsequent unresponsiveness, intractable
generalized seizure,
dysautonomia and
orofacial dyskinesia. This disorder is often accompanied by
ovarian teratoma that is originated from oocytes. Anti-neural antibody for the NR1/NR2 heteromer of NMDAR has been identified as a disease-specific hallmark. It has been emphasized that neural components in
ovarian teratoma act as a trigger to produce anti-NMDAR
antibodies, although about half of the patients with
anti-NMDAR encephalitis are not associated with
ovarian teratoma. To identify NMDAR-related
epitopes located outside of the brain, we performed immunohistochemical examinations of normal human ovary and testis using specific
antibodies against NR1, NR2A and NR2B, respectively, and found expression of the NR2B
epitope in the cytoplasm of oocytes. In contrast, the testis showed no immunohistochemical reactivity. Therefore, oocytes contain NMDAR-related
epitopes including NR2B. The NMDAR-related
epitopes in normal oocytes may cause an antigen-antibody reaction in certain pathological conditions. The presence of NR2B immunoreactivity in oocytes may account for the fact that
anti-NMDAR encephalitis predominantly affects young females.