Karrnan Pathmanandavel1, Jean Starling2, Vera Merheb1, Sudarshini Ramanathan1, Nese Sinmaz1, Russell C Dale1, Fabienne Brilot3. 1. Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead. 2. The Walker Unit, Concord Centre for Mental Health, Concord West, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia. 3. 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.
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.
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 psychoticpatients but not detected in any of 43 control subjects (p < .001). Positive immunoglobulin binding to D2R was found in 3 of 43 psychosispatients (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: Belinda R Lennox; Emma C Palmer-Cooper; Thomas Pollak; Jane Hainsworth; Jacqui Marks; Leslie Jacobson; Bethan Lang; Hannah Fox; Berne Ferry; Linda Scoriels; Hannah Crowley; Peter B Jones; Paul J Harrison; Angela Vincent Journal: Lancet Psychiatry Date: 2016-12-08 Impact factor: 27.083
Authors: Niels Hansen; Daniel Luedecke; Berend Malchow; Michael Lipp; Jonathan Vogelgsang; Charles Timäus; Tristan Zindler; Stefan Gingele; Simone Kühn; Jürgen Gallinat; Klaus Wiedemann; Johannes Denk; Nicole Moschny; Jens Fiehler; Thomas Skripuletz; Christian Riedel; Mike P Wattjes; Inga Zerr; Hermann Esselmann; Luise Poustka; Anne Karow; Hans Hartmann; Helge Frieling; Stefan Bleich; Jens Wiltfang; Alexandra Neyazi Journal: J Neural Transm (Vienna) Date: 2021-05-31 Impact factor: 3.575