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@PHDTHESIS{Leubner:144863,
      author       = {Leubner, Jonas},
      title        = {{Z}ellbasierte {T}estverfahren zur {U}ntersuchung von
                      {NMDA}-{R}ezeptor-{A}ntikörpern},
      school       = {Charité Universitätsmedizin Berlin},
      type         = {Habilitationsschrift},
      publisher    = {Charité - Universitätsmedizin Berlin},
      reportid     = {DZNE-2020-00288},
      pages        = {20 pages},
      year         = {2017},
      note         = {Habilitationsschrift, Charité Universitätsmedizin Berlin,
                      2017},
      abstract     = {Discovered in 2007, anti-N-Methyl-D-Aspartat receptor
                      (NMDAR) encephalitis is one of the most commonly identified
                      causes for encephalitis. The disease often runs a severe and
                      rapid course showing reduced state of consciousness,
                      epileptic seizures, autonomic dysregulation and hypopnea
                      leading to intensive care unit treatment and even death.
                      Clinical diagnosis is made by detection of pathogenic NMDAR
                      antibodies from a patient’s cerebrospinal fluid (CSF) or
                      serum. Little is known about prognosis factors for the
                      disease severity, but would be helpful for providing early
                      and appropriate treatment. We suppose the affinity of NMDAR
                      antibodies might be an important predicting factor. We
                      developed highly sensitive methods to detect low
                      concentrations of NMDAR antibodies, which can be used to
                      analyze antibody affinity of different patients in future.
                      Therefore, cDNA of the NR1 subunit of the NMDA receptors was
                      amplified by polymerase chain reaction, cloned into
                      different vectors and purified from Escheria coli for
                      transient and stable transfection. Immunofluorescence
                      staining on transfected HEK-cells detected lower
                      concentrations of human NMDAR antibodies than commercial
                      assays and flow cytometry showed exact quantification of the
                      antibody titer, which can be used to monitor clinical
                      progress and evaluate therapeutic success in follow-up
                      examinations. Further CSF was conjugated with Alexa Fluor
                      594 to detect human and non-human NMDA receptor antibodies
                      without secondary antibodies. The post mortem CSF analysis
                      of a young polar bear (Ursus maritimus) suffering epileptic
                      seizures showed strong binding to HEK cells expressing NMDA
                      receptors. Tissue immunohistochemistry exploration
                      demonstrated a typical neuropil signal in hippocampus and
                      cerebellum as in human patients with NMDAR encephalitis and
                      histopathological examination showed an encephalitis with
                      infiltration of plasma cells. We conclude, death was caused
                      by NMDAR encephalitis. This is the first reported non-human
                      case and suggests, that other mammals might suffer from this
                      treatable disease. Autoimmune response against neuropil
                      structures might be a basic pathomechanism across mammal
                      species.},
      keywords     = {NMDA-receptor-encephalitis (Other) / NMDAR antibodies
                      (Other) / 600 Technik, Medizin, angewandte
                      Wissenschaften::610 Medizin und Gesundheit (Other)},
      cin          = {AG Prüß},
      cid          = {I:(DE-2719)1810003},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)13},
      urn          = {urn:nbn:de:kobv:188-fudissthesis000000105584-9},
      doi          = {10.17169/REFUBIUM-6306},
      url          = {https://pub.dzne.de/record/144863},
}