title: Antibodies to surface dopamine-2 receptor and N-methyl-D-aspartate receptor in the first episode of acute psychosis in children.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead.
authors.forename: Karrnan
authors.initials: K
authors.lastname: Pathmanandavel
authors.affiliation: The Walker Unit, Concord Centre for Mental Health, Concord West, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Jean
authors.initials: J
authors.lastname: Starling
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead.
authors.forename: Vera
authors.initials: V
authors.lastname: Merheb
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead.
authors.forename: Sudarshini
authors.initials: S
authors.lastname: Ramanathan
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead.
authors.forename: Nese
authors.initials: N
authors.lastname: Sinmaz
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead. Electronic address: Fabienne.brilot@sydney.edu.au.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
mesh_terms: D000293:Adolescent; D000341:Affective Disorders, Psychotic / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood*; D002478:Cells, Cultured; D002648:Child; D015331:Cohort Studies; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011618:Psychotic Disorders / Q000276:immunology*; D017448:Receptors, Dopamine D2 / Q000276:immunology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*
chemical_list: D000906:Antibodies; C581293:DRD2 protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C409466:NR1 NMDA receptor; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Antibodies; Autoimmunity; Dopamine 2 receptor; First-episode psychosis; N-methyl-D-aspartate receptor; Schizophrenia