Autoimmune Encephalitis: NMDA Receptor Encephalitis as an Example of Translational Neuroscience

Abstract

Autoimmune encephalitis (AE) is a group of disorders causing synaptic receptor dysfunction with a broad range of neurological symptoms that has been historically difficult to differentiate clinically. Today, AE represents an excellent example of the rapid determination of the cause of a disease and the ability to identify potential treatments using relatively simple basic science techniques of investigation. Of the number of autoimmune encephalitides identified thus far, one of the best examples of the impact of basic science studies on disease management is NMDA receptor mediated autoimmune encephalitis (NMDAr-AE). In this review, we will provide an overview of the epidemiology of NMDAr-AE, clinical features and treatments, and the basic science tools and techniques that were used to identify the cause, correlate symptoms to underlying pathophysiology, and to understand the mechanism of disease pathology.

Keywords: Autoimmune encephalitis; NMDA; bench to bedside; immunotherapy; translational research.

Fig. 1

Antibody structure and approaches to labeling for immunostaining. (A) Typical antibody structure with two heavy chains and two light chains in a complex that forms two identical antigen binding regions (green sections in the yellow highlight, Fab portion). The dimer portion between heavy chains contain species-specific regions that provide epitopes for antibodies to bind and label indirectly (red FC portion). (B) Example of direct labeling of a primary antibody. A chromophore or enzyme can be attached to the heavy chain dimer portion of the primary antibody that recognizes the target antigen and provides a signal to localize the site of antigen binding interactions. (C) Example of indirect primary antibody labeling. Antibodies directed at the species-specific epitope on the heavy chain dimers can be labeled with a chromophore or enzyme and added after a primary antibody has been applied. This allows for localization of the primary antibodies and by extension the location of their binding interactions