Labeling of rat neurons by anti-GluR3 IgG from patients with Rasmussen encephalitis

Abstract

The authors report the immunocytochemical localization in rat brain of affinity-purified anti-GluR3 (glutamate receptor) antibodies from two patients with Rasmussen encephalitis (RE) and from immunized rabbits. The distribution of immunolabeling was similar using antibodies from rabbits and patients with RE. No electrophysiologic responses were elicited from acutely dissociated kainate-responsive neurons isolated from rat brain when these antibodies were applied. These findings show that anti-GluR3 antibodies purified from patients with RE bind to specific regions of the CNS but do not act through an excitotoxic mechanism.

Similar binding to glutamate receptors by Rasmussen and partial epilepsy patients’ sera

“…Interestingly, the positivity detected by ELISA and histoblot of sera from two of the patients with RE included in this study was confirmed by immunocytochemistry. 4 Immunocytochemistry is more detailed for a higher resolution, but histoblotting is simpler and straightforward giving a general overview of the antibody binding in the brain. Sera from patients with RE and PE had a staining pattern comparable to that of commercially available anti-GluR2/3 antiserum, but some differences could also be noticed: the immunolabeling was similar in the neocortex, hippocampus, basal ganglia, and cerebellum, but the thalamic labeling was not observed with anti-GluR2/3 antibody.…”

Antiglial Cell Autoantibodies and Childhood Epilepsy: A Case Report

“…Since Rogers, the physiopathologic significance of GluR3 autoantibodies has been widely discussed. The hypothesis of excitotoxicity mediated by the activation of AMPA receptors by GluR3 antibodies has not been confirmed by further studies (13,14). He et al (13) suggested that the cytotoxic effect of GluR3 antibodies might be related to a complement-mediated mechanism.…”

Autoimmune Epilepsy: Some Epilepsy Patients Harbor Autoantibodies to Glutamate Receptors and dsDNA on both Sides of the Blood‐brain Barrier, which may Kill Neurons and Decrease in Brain Fluids after Hemispherotomy

“…Specifically, anti-GluR3 Ab's were found in some patients with various types of epilepsy, suffering primarily from non-inflammatory focal epilepsy (Wiendl et al, 2001), or from severe, early-onset and intractable seizures (Mantegazza et al, 2002). Further studies and findings suggested that anti-GluR3 Ab's may indeed play a pathogenic role in epilepsy, since they can: (a) bind brain cells and structures Whitney and McNamara, 2000;Frassoni et al, 2001;Bernasconi et al, 2002), (b) activate ionotropic GluR's and evoke ion currents, acting like a "novel" glutamate agonist (Twyman et al, 1995;Koustova et al, 2001), (c) kill neurons and glia cells via excitotoxicity-a fatal overactivation of the glutamate receptors Koustova et al, 2001), alike that caused by excess glutamate in various pathological situations (Olney, 1990;Choi, 1992), and (d) activate the destructive complement system within the central nervous system (CNS), causing at first death of astrocytes, and then death of neurons (He et al, 1998;Whitney and McNamara, 2000). In this context it is of interest to mention that the serial recruitment of all the complement factors in the CNS was recently shown to induce seizures (Xiong et al, 2003).…”