Autoimmunity to glutamate receptor channels

Abstract

AbstractGlutamate and its receptors are involved in pleiotropic roles including experience‐dependent synaptic plasticity and brain development as the main fast excitatory neurotransmitters in the central nervous system. There are two main families of the glutamate receptors: (1) ionotropic glutamate receptors (iGluRs) that are ligand‐gated ion channel receptors accessible for fast synaptic transmission, and (2) metabotropic glutamate receptors (mGluRs) that are G‐protein‐coupled receptors modulating slow synaptic transmission through intracellular second messengers. Here, we summarize the current concepts of autoimmunity to these glutamate receptors in neurological disorders: anti‐GluN1 subunit of N‐methyl‐D‐aspartate receptor (NMDARs) for anti‐NMDAR encephalitis, anti‐GluA1 and GluA2 subunits of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPARs) for anti‐AMPAR encephalitis, and anti‐mGluR5 subunit for Ophelia syndrome. Most identified autoimmunity to glutamate receptors can lead to unique synaptopathies or neuronal antibody‐mediated encephalopathies. Evidence‐based optimal management guidelines and new disease‐modifying therapies need to be developed for patients with autoimmune encephalitis including anti‐glutamate receptor encephalitis.