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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},
}