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@ARTICLE{Preler:280045,
author = {Preßler, Hannah and Bünger, Isabel and Prüss, Harald},
title = {{N}ovel cerebrospinal fluid anti-central nervous system
{I}g{G} antibodies can identify immunotherapy-responsive
neuropsychiatric disorders.},
journal = {Frontiers in immunology},
volume = {16},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DZNE-2025-00884},
pages = {1612844},
year = {2025},
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.},
keywords = {Humans / Autoantibodies: cerebrospinal fluid /
Autoantibodies: immunology / Female / Immunoglobulin G:
cerebrospinal fluid / Immunoglobulin G: immunology / Male /
Middle Aged / Retrospective Studies / Immunotherapy: methods
/ Adult / Animals / Aged / Mice / Mental Disorders:
cerebrospinal fluid / Mental Disorders: immunology / Mental
Disorders: therapy / Mental Disorders: diagnosis / Young
Adult / Biomarkers: cerebrospinal fluid / Adolescent /
Central Nervous System: immunology / autoimmune neurology
and psychiatry (Other) / immunofluorescence (Other) /
immunotherapy (Other) / novel anti neuronal autoantibodies
(Other) / seronegative autoimmune encephalitis (Other) /
Autoantibodies (NLM Chemicals) / Immunoglobulin G (NLM
Chemicals) / Biomarkers (NLM Chemicals)},
cin = {AG Prüß},
ddc = {610},
cid = {I:(DE-2719)1810003},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40692787},
pmc = {pmc:PMC12277280},
doi = {10.3389/fimmu.2025.1612844},
url = {https://pub.dzne.de/record/280045},
}