Home > Publications Database > Novel cerebrospinal fluid anti-central nervous system IgG antibodies can identify immunotherapy-responsive neuropsychiatric disorders. > print

001     280045
005     20250824001725.0
024 7 _ |a 10.3389/fimmu.2025.1612844
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037 _ _ |a DZNE-2025-00884
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Preßler, Hannah
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245 _ _ |a Novel cerebrospinal fluid anti-central nervous system IgG antibodies can identify immunotherapy-responsive neuropsychiatric disorders.
260 _ _ |a Lausanne
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|b Frontiers Media
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520 _ _ |a 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.
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650 _ 7 |a autoimmune neurology and psychiatry
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650 _ 7 |a immunofluorescence
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650 _ 7 |a immunotherapy
|2 Other
650 _ 7 |a novel anti neuronal autoantibodies
|2 Other
650 _ 7 |a seronegative autoimmune encephalitis
|2 Other
650 _ 7 |a Autoantibodies
|2 NLM Chemicals
650 _ 7 |a Immunoglobulin G
|2 NLM Chemicals
650 _ 7 |a Biomarkers
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Autoantibodies: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Autoantibodies: immunology
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Immunoglobulin G: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Immunoglobulin G: immunology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
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650 _ 2 |a Retrospective Studies
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650 _ 2 |a Immunotherapy: methods
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650 _ 2 |a Adult
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650 _ 2 |a Animals
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650 _ 2 |a Aged
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650 _ 2 |a Mice
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650 _ 2 |a Mental Disorders: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Mental Disorders: immunology
|2 MeSH
650 _ 2 |a Mental Disorders: therapy
|2 MeSH
650 _ 2 |a Mental Disorders: diagnosis
|2 MeSH
650 _ 2 |a Young Adult
|2 MeSH
650 _ 2 |a Biomarkers: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Adolescent
|2 MeSH
650 _ 2 |a Central Nervous System: immunology
|2 MeSH
700 1 _ |a Bünger, Isabel
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700 1 _ |a Prüss, Harald
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773 _ _ |a 10.3389/fimmu.2025.1612844
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