Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis

Abstract Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesi...

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Autores principales:	Jakob Theorell, Melanie Ramberger, Ruby Harrison, Victor Mgbachi, Leslie Jacobson, Patrick Waters, Sophie Erhardt, Carl M. Sellgren, Simon Cervenka, Fredrik Piehl, Sarosh R. Irani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/670d503e5658437984cbb09c99860bba
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spelling	oai:doaj.org-article:670d503e5658437984cbb09c99860bba2021-11-07T12:17:38ZScreening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis10.1038/s41398-021-01701-32158-3188https://doaj.org/article/670d503e5658437984cbb09c99860bba2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01701-3https://doaj.org/toc/2158-3188Abstract Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised that a subgroup of patients with first-episode psychosis (FEP) suffer from a forme fruste of autoimmune encephalitis. Without accurate identification, this immunotherapy-responsive subgroup may be denied disease-modifying treatments. Thirty studies addressing aspects of this hypothesis were identified in a systematic review. Amongst other shortcomings, 15/30 reported no control group and only 6/30 determined cerebrospinal fluid (CSF) autoantibodies. To ourselves address these—and other—limitations, we investigated a prospectively ascertained clinically well-characterised cohort of 71 FEP patients without traditional neurological features, and 48 healthy controls. Serum and CSF were tested for autoantibodies against seven neuronal surface autoantigens using live cell-based assays. These identified 3/71 (4%) patient sera with weak binding to either contactin-associated protein-like 2, the NMDAR or glycine receptor versus no binding from 48 control samples (p = 0.28, Fisher’s test). The three seropositive individuals showed no CSF autoantibodies and no differences from the autoantibody-negative patients in their clinical phenotypes, or across multiple parameters of peripheral and central inflammation. All individuals were negative for CSF NMDAR antibodies. In conclusion, formes frustes of autoimmune encephalitis are not prevalent among FEP patients admitted to psychiatric care. Our findings do not support screening for neuronal surface autoantibodies in unselected psychotic patients.Jakob TheorellMelanie RambergerRuby HarrisonVictor MgbachiLeslie JacobsonPatrick WatersSophie ErhardtCarl M. SellgrenSimon CervenkaFredrik PiehlSarosh R. IraniNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jakob Theorell Melanie Ramberger Ruby Harrison Victor Mgbachi Leslie Jacobson Patrick Waters Sophie Erhardt Carl M. Sellgren Simon Cervenka Fredrik Piehl Sarosh R. Irani Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis
description	Abstract Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised that a subgroup of patients with first-episode psychosis (FEP) suffer from a forme fruste of autoimmune encephalitis. Without accurate identification, this immunotherapy-responsive subgroup may be denied disease-modifying treatments. Thirty studies addressing aspects of this hypothesis were identified in a systematic review. Amongst other shortcomings, 15/30 reported no control group and only 6/30 determined cerebrospinal fluid (CSF) autoantibodies. To ourselves address these—and other—limitations, we investigated a prospectively ascertained clinically well-characterised cohort of 71 FEP patients without traditional neurological features, and 48 healthy controls. Serum and CSF were tested for autoantibodies against seven neuronal surface autoantigens using live cell-based assays. These identified 3/71 (4%) patient sera with weak binding to either contactin-associated protein-like 2, the NMDAR or glycine receptor versus no binding from 48 control samples (p = 0.28, Fisher’s test). The three seropositive individuals showed no CSF autoantibodies and no differences from the autoantibody-negative patients in their clinical phenotypes, or across multiple parameters of peripheral and central inflammation. All individuals were negative for CSF NMDAR antibodies. In conclusion, formes frustes of autoimmune encephalitis are not prevalent among FEP patients admitted to psychiatric care. Our findings do not support screening for neuronal surface autoantibodies in unselected psychotic patients.
format	article
author	Jakob Theorell Melanie Ramberger Ruby Harrison Victor Mgbachi Leslie Jacobson Patrick Waters Sophie Erhardt Carl M. Sellgren Simon Cervenka Fredrik Piehl Sarosh R. Irani
author_facet	Jakob Theorell Melanie Ramberger Ruby Harrison Victor Mgbachi Leslie Jacobson Patrick Waters Sophie Erhardt Carl M. Sellgren Simon Cervenka Fredrik Piehl Sarosh R. Irani
author_sort	Jakob Theorell
title	Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis
title_short	Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis
title_full	Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis
title_fullStr	Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis
title_full_unstemmed	Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis
title_sort	screening for pathogenic neuronal autoantibodies in serum and csf of patients with first-episode psychosis
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/670d503e5658437984cbb09c99860bba
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Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis

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