Journal Article

DZNE-2025-00884

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Novel cerebrospinal fluid anti-central nervous system IgG antibodies can identify immunotherapy-responsive neuropsychiatric disorders.

Preßler, H. (First author)DZNE* ; Bünger, I.DZNE* ; Prüss, H. (Last author)DZNE*

2025
Frontiers Media Lausanne

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Please use a persistent id in citations: doi:10.3389/fimmu.2025.1612844

Abstract: Autoantibodies (Abs) targeting the central nervous system (CNS) can cause various neuropsychiatric autoimmune diseases. The potential response to immunotherapy necessitates the continuous expansion of Ab testing strategies including non-antigen-specific screening assays. This study investigated whether tissue-based screening using unfixed murine CNS sections can help to identify patients with immunotherapy-responsive neuropsychiatric diseases after routine Ab panels yielded negative results.This retrospective single-center study screened cerebrospinal fluid (CSF) of 279 patients for immunoglobulin G (IgG) anti-CNS Abs using unfixed mouse brain. Patients had a variety of neuropsychiatric conditions, in which an autoimmune contribution was considered. Previous testing for a panel of established autoantibodies using cell-based assays remained negative. Of 238 patients, paired serum samples were available.A subgroup of 55 patients (20%) showed novel anti-CNS autoantibody patterns in CSF, consisting of anti-myelin (n=13), anti-neuropil (n=14), anti-vessel (n=8), anti-tight junction (n=5), anti-cellular (n=8), and anti-astroglial (n=7) autoantibodies. Thirty-six patients (65%) fulfilled criteria for possible, probable, or definite autoimmune encephalitis or paraneoplastic neurological syndrome. Memory impairment (73%) and psychiatric abnormalities (64%) were the most frequent symptoms. Antibody subtypes were not significantly associated with clinical parameters at this sample size, however, there was a trend towards better response to immunotherapy with antibodies against myelin, neuropil, and neuronal cells, while patients with anti-vessel antibodies did not improve. CNS autoantibodies mainly disappeared parallel to clinical improvement. In 46% of treated patients, physicians would not have started immunotherapy without detection of anti-CNS autoantibodies, and the vast majority of patients stabilized or improved.Novel CNS Abs were common in patients with suspected 'seronegative' autoimmune neuropsychiatric disorders. Detection facilitated identification of immunotherapy-responsive cases and enabled treatment initiation without increasing unnecessary treatments. Thus, tissue screening using unfixed mouse brain applied in patients with suspected neuropsychiatric autoimmune diseases parallel to established cell-based assays. Future studies should identify the underlying antigens, demonstrate the pathogenic role in animal models, and implement promising Abs into diagnostic routine panels.

Keyword(s): Humans (MeSH) ; Autoantibodies: cerebrospinal fluid (MeSH) ; Autoantibodies: immunology (MeSH) ; Female (MeSH) ; Immunoglobulin G: cerebrospinal fluid (MeSH) ; Immunoglobulin G: immunology (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Retrospective Studies (MeSH) ; Immunotherapy: methods (MeSH) ; Adult (MeSH) ; Animals (MeSH) ; Aged (MeSH) ; Mice (MeSH) ; Mental Disorders: cerebrospinal fluid (MeSH) ; Mental Disorders: immunology (MeSH) ; Mental Disorders: therapy (MeSH) ; Mental Disorders: diagnosis (MeSH) ; Young Adult (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Adolescent (MeSH) ; Central Nervous System: immunology (MeSH) ; autoimmune neurology and psychiatry ; immunofluorescence ; immunotherapy ; novel anti neuronal autoantibodies ; seronegative autoimmune encephalitis ; Autoantibodies ; Immunoglobulin G ; Biomarkers

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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