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000280045 1001_ $$0P:(DE-2719)9003388$$aPreßler, Hannah$$b0$$eFirst author$$udzne
000280045 245__ $$aNovel cerebrospinal fluid anti-central nervous system IgG antibodies can identify immunotherapy-responsive neuropsychiatric disorders.
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000280045 520__ $$aAutoantibodies (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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000280045 650_7 $$2Other$$aautoimmune neurology and psychiatry
000280045 650_7 $$2Other$$aimmunofluorescence
000280045 650_7 $$2Other$$aimmunotherapy
000280045 650_7 $$2Other$$anovel anti neuronal autoantibodies
000280045 650_7 $$2Other$$aseronegative autoimmune encephalitis
000280045 650_7 $$2NLM Chemicals$$aAutoantibodies
000280045 650_7 $$2NLM Chemicals$$aImmunoglobulin G
000280045 650_7 $$2NLM Chemicals$$aBiomarkers
000280045 650_2 $$2MeSH$$aHumans
000280045 650_2 $$2MeSH$$aAutoantibodies: cerebrospinal fluid
000280045 650_2 $$2MeSH$$aAutoantibodies: immunology
000280045 650_2 $$2MeSH$$aFemale
000280045 650_2 $$2MeSH$$aImmunoglobulin G: cerebrospinal fluid
000280045 650_2 $$2MeSH$$aImmunoglobulin G: immunology
000280045 650_2 $$2MeSH$$aMale
000280045 650_2 $$2MeSH$$aMiddle Aged
000280045 650_2 $$2MeSH$$aRetrospective Studies
000280045 650_2 $$2MeSH$$aImmunotherapy: methods
000280045 650_2 $$2MeSH$$aAdult
000280045 650_2 $$2MeSH$$aAnimals
000280045 650_2 $$2MeSH$$aAged
000280045 650_2 $$2MeSH$$aMice
000280045 650_2 $$2MeSH$$aMental Disorders: cerebrospinal fluid
000280045 650_2 $$2MeSH$$aMental Disorders: immunology
000280045 650_2 $$2MeSH$$aMental Disorders: therapy
000280045 650_2 $$2MeSH$$aMental Disorders: diagnosis
000280045 650_2 $$2MeSH$$aYoung Adult
000280045 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000280045 650_2 $$2MeSH$$aAdolescent
000280045 650_2 $$2MeSH$$aCentral Nervous System: immunology
000280045 7001_ $$0P:(DE-2719)9002228$$aBünger, Isabel$$b1
000280045 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b2$$eLast author$$udzne
000280045 773__ $$0PERI:(DE-600)2606827-8$$a10.3389/fimmu.2025.1612844$$gVol. 16, p. 1612844$$p1612844$$tFrontiers in immunology$$v16$$x1664-3224$$y2025
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