The diverse and complex modes of action of anti-NMDA receptor autoantibodies. (15th August 2021)

• Record Type: Journal Article
• Authors: Wollmuth, Lonnie P.; Chan, Kelvin; Groc, Laurent
• Is Part Of: Neuropharmacology. Volume 194(2021)
• Publication Date: 2021-08-15
• Subjects: Anti-NMDA receptor Encephalitis -- Systemic lupus erythematosus (SLE) -- Neuropsychiatric lupus (NPLSE); Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108624
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: NMDA receptors are ligand-gated ion channels that are found throughout the brain and are required for both brain development and many higher order functions. A variety of human patients with diverse clinical phenotypes have been identified that carry autoantibodies directed against NMDA receptor subunits. Here we focus on two general classes of autoantibodies, anti-GluN1 antibodies associated with anti-NMDA receptor encephalitis and anti-GluN2 antibodies associated with systemic lupus erythematosus (SLE). These two general classes of anti-NMDA receptor autoantibodies display a wide range of pathophysiological mechanisms from altering synaptic composition to gating of NMDARs. While we have made progress in understanding how these autoantibodies work at the molecular and cellular level, many unanswered questions remain including their long-term actions on brain function, the significance of clonal variations, and their effects on different NMDA receptor-expressing cell types in local circuits. This information will be needed to define fully the transition from anti-NMDA receptor autoantibodies to a clinical phenotype. This article is part of the Neuropharmacology Special Issue on 'Glutamate Receptors – NMDA receptors'. Graphical abstract: Autoantibodies that target the NMDA receptor can alter their cell biology – anti-GluN1 – and/or functional properties – anti-GluN2 – and potentially lead to disease states. Image 1 Highlights: Autoantibodies against NMDA receptor subunits are associated with various clinical phenotypes. The molecular and cellular actions of these autoantibodies appear heterogeneous. Many aspects of how these autoantibodies act on single cells and circuits is poorly known. A greater understanding of these autoantibodies may guide potential treatments.