Antibodies to Surface Dopamine-2 Receptor and N-Methyl-D-Aspartate Receptor in the First Episode of Acute Psychosis in Children

• Published in: Biological psychiatry (1969) Vol. 77; no. 6; pp. 537 - 547
• Main Authors: Pathmanandavel, Karrnan, Starling, Jean, Merheb, Vera, Ramanathan, Sudarshini, Sinmaz, Nese, Dale, Russell C., Brilot, Fabienne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2015
• Subjects: Adolescent; Affective Disorders, Psychotic - immunology; Animals; Antibodies; Antibodies - blood; Autoimmunity; Cells, Cultured; Child; Cohort Studies; Dopamine 2 receptor; Female; First-episode psychosis; HEK293 Cells; Hippocampus - metabolism; Humans; Immunoglobulin A - blood; Immunoglobulin G - blood; Immunoglobulin M - blood; Male; Mice; N-methyl-D-aspartate receptor; Neurons - metabolism; Psychiatric/Mental Health; Psychotic Disorders - immunology; Receptors, Dopamine D2 - immunology; Receptors, N-Methyl-D-Aspartate - immunology; Schizophrenia; Autoimmunity; Dopamine 2 receptor; Antibodies; N-methyl-D-aspartate receptor; Schizophrenia; First-episode psychosis
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2014.07.014

The dopamine and glutamate hypotheses are well known in psychosis. Recently, the detection of autoantibodies against proteins expressed on the surface of cells in the central nervous system has raised the possibility that specific immune-mediated mechanisms may define a biological subgroup within psychosis, although no cohort of a first episode of psychosis in children has been investigated. Serum taken during the acute presentation of 43 children with first episode of psychosis and serum from 43 pediatric control subjects was assessed for the presence of immunoglobulin (Ig)G, IgM, or IgA antibodies to dopamine-2 receptor (D2R) and NR1 subunit of the N-methyl-D-aspartate receptor using a flow cytometry live cell-based assay and immunolabeling of murine primary neurons. Using a cutoff of three SD above the control mean, serum antibodies to D2R or NR1 were detected in 8 of 43 psychotic patients but not detected in any of 43 control subjects (p < .001). Positive immunoglobulin binding to D2R was found in 3 of 43 psychosis patients (3 IgG, 1 IgM, 0 IgA) and to N-methyl-D-aspartate receptor in 6 of 43 patients (5 IgG, 1 IgM, 1 IgA). Specificity of antibody was confirmed by immunoaffinity purification and immunoabsorption. Significant differences in antibody binding to live, fixed, and fixed and permeabilized neurons were observed, confirming that only live cells can define surface epitope immunolabeling. This is the first report of serum antibodies to surface D2R and NR1 in pediatric patients with isolated psychosis, which supports the hypothesis that a subgroup of patients may be immune-mediated.