No evidence for the presence of neuronal surface autoantibodies in plasma of patients with schizophrenia

Mierlo, Hans C. van; Coevorden-Hameete, Marleen H. van; Munting, Leon P; Graaff, Esther de; Witte, Lot de

doi:10.1016/j.euroneuro.2015.09.017

Cited by 8 publications

(6 citation statements)

References 28 publications

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“…Results have been less compelling for anti-AMPAR antibodies, as the majority of studies have been negative [10, 15, 18, 20, 23, 26, 28, 29]. Moreover, in each of the two positive studies, antibodies were found in only one patient (<1% of the samples) [11, 24], and the only study that included a healthy control group also found antibodies in 0.2% of controls [11].…”

Section: Resultsmentioning

confidence: 99%

“…The majority of negative studies also used the same aforementioned commercially available CBA (or a modification of it) [17-22, 24-29], and four of these studies also included immunohistochemistry for further testing [19, 26-28]. Two negative studies, including one previously referenced study that also used the commercial CBA kit for testing some of its sample, used in-house CBAs [22, 23]. Similarly, consideration of the antibody detection method used in only those positive studies that included a healthy control group for comparison is mostly unrevealing.…”

Section: Resultsmentioning

confidence: 99%

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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%

Section: Resultsmentioning

confidence: 99%

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

Colijn

Ismail

2019

Neuropsychobiology

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“…This chance quickly increases if patients develop neurological symptoms or additional features such as fever or autonomic dysfunction. In studies testing for anti-NMDAR IgG in a purely psychiatric population using more than one method (CBA combined with IHC or ICC of living hippocampal neurons, or the combination of serum and CSF) no patients with only psychiatric features and anti-NMDAR encephalitis have been found (Masdeu et al, 2012 ; van Mierlo et al, 2015 ). The low a priori chance in patients with psychiatric disorders combined with a specificity of 97–99.4% for CBA of serum (Gresa-Arribas et al, 2014 ) results in a post priori chance of only 25–60% when testing serum only.…”

Section: Cell Based Assaysmentioning

confidence: 99%

Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System

Coevorden-Hameete

Titulaer

Schreurs

et al. 2016

Front. Mol. Neurosci.

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Autoimmune encephalitis (AIE) is a group of disorders in which autoantibodies directed at antigens located on the plasma membrane of neurons induce severe neurological symptoms. In contrast to classical paraneoplastic disorders, AIE patients respond well to immunotherapy. The detection of neuronal surface autoantibodies in patients’ serum or CSF therefore has serious consequences for the patients’ treatment and follow-up and requires the availability of sensitive and specific diagnostic tests. This mini-review provides a guideline for both diagnostic and research laboratories that work on the detection of known surface autoantibodies and/or the identification of novel surface antigens. We discuss the strengths and pitfalls of different techniques for anti-neuronal antibody detection: (1) Immunohistochemistry (IHC) and immunofluorescence on rat/primate brain sections; (2) Immunocytochemistry (ICC) of living cultured hippocampal neurons; and (3) Cell Based Assay (CBA). In addition, we discuss the use of immunoprecipitation and mass spectrometry analysis for the detection of novel neuronal surface antigens, which is a crucial step in further disease classification and the development of novel CBAs.

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“…Mantere et al [39] revealed 1 positive case in the group of participants with clinical high risk for psychosis, who had not converted to psychosis but remained AB positive at 1-year follow-up. The other studies failed to find any positive cases in patient [25, 68] and control [25, 39] groups.…”

Section: Resultsmentioning

confidence: 95%

“…Six studies did not specify the subunit of NMDAR against which the ABs they looked for were directed [25, 39, 65-68]. Coutinho et al [65] found 7.5 and 4.3% of positive cases in patient group and controls, respectively, by live CBA (while 5 other studies used fixed CBA).…”

Section: Resultsmentioning

confidence: 99%

Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review

et al. 2021

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Objective: The objective of this study was to provide comprehensive evidence synthesis including all available up-to-date data about the prevalence of N-methyl D-aspartate receptor (NMDAR) antibodies (ABs) in psychotic patients in order to evaluate the clinical relevance of ABs as well as to specify potential explanations of the heterogeneity of the findings and determine areas for further research. Methods: A literature search was conducted using the PubMed/Medline, Web of Knowledge, and Scopus databases. Results: Forty-seven studies and 4 systematic reviews (including 2 meta-analyses) were included in the present review. Studies that used cell-based assays (CBAs) provided heterogeneous results on AB prevalence, obviously depending on the type of detection assay and sample characteristics. Improvement of AB detection methods is necessary to determine the real prevalence of ABs across different groups of patients and healthy people. Live CBAs seem to have better sensitivity but probably poorer specificity than fixed CBAs. Moreover, some links between AB-positive status and acute symptoms are possible. A small amount of data on immunotherapy in AB-positive patients raises the possibility of its effectiveness but obviously require further research. Conclusions: NMDAR ABs are definitely present in a subset of psychotic patients. NMDAR ABs might shape psychosis and underlie some symptoms, and immunotherapy might be regarded as a treatment option for patients failing to respond to other therapies.

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No evidence for the presence of neuronal surface autoantibodies in plasma of patients with schizophrenia

Cited by 8 publications

References 28 publications

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

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

Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System

Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review

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