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

Pathmanandavel, Karrnan; Starling, Jean; Merheb, Vera; Ramanathan, Sudarshini; Sinmaz, Nese; Dale, Russell C.; Brilot, Fabienne

doi:10.1016/j.biopsych.2014.07.014

Cited by 92 publications

(110 citation statements)

References 56 publications

(101 reference statements)

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“…The frequency of antibody positivity was around 5% or less in all but one study [13] and was less than 1% in two studies [11, 12]. Of the studies that produced positive results, five included a healthy control group for comparison [10-13, 15], and two of these studies, in addition to further testing in one of them, also identified antibodies in 0.4–1.2% of healthy controls [11, 12, 30], making interpretation of the results difficult. No group differences in seroprevalence were found, where reported.…”

Section: Resultsmentioning

confidence: 99%

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Colijn

Ismail

2019

Neuropsychobiology

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Schizophrenia is a phenotypically heterogeneous and poorly understood disorder. While its etiology is likely multifactorial, immune system dysfunction has increasingly been implicated in its development. As hallucinations and delusions occur frequently and prominently in autoimmune encephalitis (AE), numerous studies have sought to determine whether a small subset of individuals diagnosed with schizophrenia possess anti-neuronal antibodies implicated in AE. Exploring this possibility is of clinical relevance, as identifying individuals with AE who have been misdiagnosed as having a primary psychotic disorder may allow for the implementation of appropriate immune-related therapies as early as possible in the course of the illness, in order to optimize outcomes, reduce illness chronicity, and minimize adverse events. This qualitative review serves to provide an overview of the existing literature on this topic, as well as to update previously published reviews. Although there is some evidence to suggest that in rare cases AE may be misdiagnosed as a primary psychotic disorder, particularly early in the course of the illness, numerous methodological differences between studies likely account for the highly variable findings, and interpretation of the results is particularly limited by a paucity of cerebrospinal fluid data. Moreover, the prevalence of misdiagnosis in chronic and treatment-resistant populations remains understudied. This is particularly problematic, as treatment resistance may represent an enriched population with respect to the presence of anti-neuronal antibodies, and given that such patients have few evidence-based treatment options available to them beyond clozapine.

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Section: Resultsmentioning

confidence: 99%

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Colijn

Ismail

2019

Neuropsychobiology

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“…Curiously, only the two patients with anti-GluN1 IgG autoantibodies presented IgG positive titers in CSF, a controversial result based on the 3.2% reactivity to neuronal surface antigens in CSF found in a psychotic disorder cohort (0.8% to NMDA-R and 2.4% to VGKC complex) [144]. Another study showed GluN1 IgG autoantibodies in 5 out of 43 children with a first episode of acute psychosis, screened by a more objective variety of the CBA using flow cytometry [160]. This subunit was also recognized by IgA or IgM [160] but not specifically related with schizophrenia, since they were also present in other pathologies and in control individuals [121,159].…”

Section: Psychotic Disordersmentioning

confidence: 99%

“…Nevertheless, the results are controversial, since a number of other studies did not find autoantibodies in neuropsychiatric cohorts [146,159,162,163] or not specific to the disease [45,122]. New and more objective techniques, like flow cytometry CBA, are being introduced to the research routine [129,160], but a standardized procedure to screen patients for neuronal surface antigens needs to be defined to reduce results variability.…”

Section: Psychotic Disordersmentioning

confidence: 99%

“…Another study showed GluN1 IgG autoantibodies in 5 out of 43 children with a first episode of acute psychosis, screened by a more objective variety of the CBA using flow cytometry [160]. This subunit was also recognized by IgA or IgM [160] but not specifically related with schizophrenia, since they were also present in other pathologies and in control individuals [121,159]. IgA autoantibodies to NMDA-R (but not IgG) were described in a cognitive dysfunction cohort where they are thought to induce decreased NMDA-R expression and NMDA-R mediated currents in neuronal cell cultures [120].…”

Section: Psychotic Disordersmentioning

confidence: 99%

“…On the other hand, the presence of autoantibodies to any class of the GABA-R has not been studied in psychotic disorders to our knowledge. The D2DR autoantibodies have been described in a cohort of first episode acute psychosis children (3 out of 43 IgG and 1 out of 43 IgM subtypes) [160].…”

Section: Psychotic Disordersmentioning

confidence: 99%

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Autoantibodies in Neuropsychiatric Disorders

et al. 2016

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Abstract:Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-D-aspartate receptor (NMDA-R), which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition. In recent years, a wide range of neuropsychiatric diseases and autoantibodies targeting ion-channels or neuronal receptors including NMDA-R, voltage gated potassium channel complex (VGKC complex), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R), γ-aminobutyric acid receptor (GABA-R) and dopamine receptor (DR) were studied and conflicting reports have been published regarding the seroprevalence of these autoantibodies. A clear causative role of autoantibodies on psychiatric symptoms has as yet only been shown for the NMDA-R. Several other autoantibodies have been related to the presence of certain symptoms and antibody effector mechanisms have been proposed. However, extensive clinical studies with large multicenter efforts to standardize diagnostic procedures for autoimmune etiology and animal studies are needed to confirm the pathogenicity of these autoantibodies. In this review, we discuss the current knowledge of neuronal autoantibodies in the major neuropsychiatric disorders: psychotic, major depression, autism spectrum, obsessive-compulsive and attention-deficit/hyperactivity disorders.

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Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

et al. 2020

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Objectives A dysregulated inflammatory response against the dopamine‐2 receptor (D2R) has been implicated in movement and psychiatric disorders. D2R antibodies were previously reported in a subset of these patients; however, the role of T cells in these disorders remains unknown. Our objective was to identify and characterise pro‐inflammatory D2R‐specific T cells in movement and psychiatric disorders. Methods Blood from paediatric patients with movement and psychiatric disorders of suspected autoimmune and neurodevelopmental aetiology (n = 24) and controls (n = 16) was cultured in vitro with a human D2R peptide library, and D2R‐specific T cells were identified by flow cytometric quantification of CD4+CD25+CD134+ T cells. Cytokine secretion was analysed using a cytometric bead array and ELISA. HLA genotypes were examined in D2R‐specific T‐cell‐positive patients. D2R antibody seropositivity was determined using a flow cytometry live cell‐based assay. Results Three immunodominant regions of D2R, amino acid (aa)121–131, aa171–181 and aa396–416, specifically activated CD4+ T cells in 8/24 patients. Peptides corresponding to these regions were predicted to bind with high affinity to the HLA of the eight positive patients and had also elicited the secretion of pro‐inflammatory cytokines IL‐2, IFN‐ γ, TNF, IL‐6, IL‐17A and IL‐17F. All eight patients were seronegative for D2R antibodies. Conclusion Autoreactive D2R‐specific T cells and a pro‐inflammatory Th1 and Th17 cytokine profile characterise a subset of paediatric patients with movement and psychiatric disorders, further underpinning the theory of immune dysregulation in these disorders. These findings offer new perspectives into the neuroinflammatory mechanisms of movement and psychiatric disorders and can influence patient diagnosis and treatment.

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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

Cited by 92 publications

References 56 publications

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

Autoantibodies in Neuropsychiatric Disorders

Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

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