Detection of antibodies against the N-methyl-d-aspartate receptor in a sub-group of patients diagnosed with Tourette's syndrome

Background: The N-methyl-D-aspartate receptor (NMDAR) is a type of ionotropic receptor belonging to the glutamate receptor superfamily found abundantly in the cortex, basal ganglia, and sensory pathways of the nervous system. The receptor is highly permeable to calcium ions and plays a key role in the plasticity of synapses, which is believed to underlie memory and learning. The NMDAR has been associated with a range of neurological disorders including ischemic brain damage and epilepsy, andmore speculatively with neurodegenerative disorders such as Alzheimer's and Huntington's chorea. Anti-NMDA receptor encephalitis has been recently identified as treatment responsive encephalitis associatedwith anti-NMDA receptor antibodies (Iizuka and Sakai, 2008). These antibodies bind to the NR1/NR2 heteromers of the NMDAR and antibody levels are known to correlate with the clinical severity of the disease. Clinical features seen in neuropsychiatric disorders such as Tourette's syndrome (TS) overlap with NMDAR receptor encephalitis, which might make it a part of the spectrum of anti-NMDAR disorders. Aims: Pathogenic antibodies against the NMDAR have been implicated in a range of disorders, however, the full clinical spectrum and treatment responses are still unclear. Therefore, in the present study we analysed serum samples from children diagnosed with TS for the presence of anti-NMDAR antibodies. Materials and methods: Sera from 21 TS patients with a mean age of 11 years were analysed for the presence of antibodies against the NMDAR using HEK293 cells transfected with NR1:NR2B subunits and co-transfected with enhanced green fluorescent protein (EGFP). According to the number of cells stained and intensity of staining the samples were scored between 0 and 4 (0= negative, 4= strongly positive). Results: Out of the 21 samples tested in the assay 4 were found positive for antibodies against the NMDAR. All 4 serum samples came frommale patients diagnosed with TS with an age range of 8 to 14 years. Conclusions: In the present study the presence of anti-NMDAR antibodies in the sera of 4 TS patients has been demonstrated. TS is co-morbid with multiple conditions like obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) so an understanding into its pathogenic mechanism would have major implications in the field of neuropsychiatry.