Proteome Remodeling in a Peptide Immunization Animal Model of Anti-NMDAR Encephalitis

Abstract

Anti-NMDAR encephalitis is the most common subtype of autoimmune encephalitis (AIE) and is characterized by GluN1 antibodies. Disease is associated with substantial morbidity and mortality, highlighting critical unmet therapeutic needs. Most animal models of anti-NMDAR encephalitis depend on intracerebroventricular transfer of patient-derived antibodies or cerebrospinal fluid (CSF), or immunization with structurally intact NMDARs. However, recent studies have demonstrated the induction of anti-NMDAR encephalitis in rodent models through GluN1 peptide immunization, with differing effects. Anti-NMDAR antibodies target the amino terminal domain of the GluN1 subunit, and cause receptor loss and associated neuropsychiatric symptoms such as memory impairment, psychosis, and seizures with high morbidity and mortality. The immunopathogenesis remains unclear and therapeutic management of anti-NMDAR encephalitis have been limited by incomplete knowledge of its pathogenesis.