Autoantibodies to glutamate receptors can damage the brain in epilepsy, systemic lupus erythematosus and encephalitis.
Glutamate is the major excitatory CNS neurotransmitter. Glutamate receptor autoantibodies have now been called to our attention, as they are found in many patients with epilepsy, systemic lupus erythematosus (SLE) and encephalitis, and can unquestionably cause brain damage. AMPA GluR3 autoantibodies have been found thus far in 27% of patients with different epilepsies, while NMDA NR2A or NR2B autoantibodies, some of which cross-react with double-stranded DNA, have been detected in 30% of SLE patients, with or without neuropsychiatric impairments. NR2 autoantibodies were also found in patients with epilepsy (33%), encephalitis and stroke. NR2 and GluR3 autoantibodies do not cross-react in patients with epilepsy. Human and animal studies show that both types of glutamate receptor autoantibodies can certainly damage the brain. GluR3 autoantibodies bind to neurons, possess a unique ability to activate their glutamate-receptor antigen, and cause neuronal death (either by excitotoxicity or by complement fixation independent of receptor activation), multiple brain damage and neurobehavioral/cognitive impairments. In animal models (mice, rats or rabbits) GluR3 autoantibodies may cause seizures, augment their severity or modulate their threshold. NR2/dsDNA autoantibodies, once present in the CNS, can bind and subsequently kill hippocampal and cortical neurons by an excitotoxic complement-independent mechanism. Herein, we discuss epilepsy, autoimmune epilepsy, SLE and neuropsychiatric SLE in general; summarize the up-to-date in vivo and in vitro evidence concerning the presence of glutamate receptor autoantibodies in human diseases; discuss the activity and pathogenicity of different glutamate receptor autoantibodies; and end with our conclusions, recommendations and suggested future directions.
Levite
Mia
M
School of Behavioral Sciences, Academic College of TLV Yaffo, Israel; The Weizmann Institue of Science, Rehovot 76100, Israel. mia.levite@weizmann.ac.il
Ganor
Yonatan
Y
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001930:Brain Injuries / Q000209:etiology*; D004660:Encephalitis / Q000097:blood / Q000150:complications / Q000276:immunology; D004827:Epilepsy / Q000097:blood / Q000150:complications* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology; D017470:Receptors, Glutamate / Q000276:immunology*
D001323:Autoantibodies; D017470:Receptors, Glutamate