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

  • Karrnan Pathmanandavel
    Affiliations
    Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead
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  • Jean Starling
    Affiliations
    The Walker Unit, Concord Centre for Mental Health, Concord West, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia.
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  • Vera Merheb
    Affiliations
    Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead
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  • Sudarshini Ramanathan
    Affiliations
    Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead
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  • Nese Sinmaz
    Affiliations
    Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead
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  • Russell C. Dale
    Affiliations
    Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead
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  • Fabienne Brilot
    Correspondence
    Address correspondence to Fabienne Brilot, Ph.D., Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead, University of Sydney, Locked Bag 4001, Westmead Sydney, NSW 2145, Australia
    Affiliations
    Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead
    Search for articles by this author

      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.

      Keywords

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