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@ARTICLE{Kreye:280960,
      author       = {Kreye, Jakob and Morgenlander, William R and Thakar,
                      Manjusha and Schulte-Frankenfeld, Poul M and Schott, Sarah
                      and Bünger, Isabel and Kornau, Hans-Christian and Angkeow,
                      Julia W and Jayaraman, Sahana and Otto, Carolin and Hahn,
                      Wiebke and Lewerenz, Jan and Thaler, Franziska S and
                      Korporal-Kuhnke, Mirjam and Melzer, Nico and Dargvainiene,
                      Justina and Bien, Christian G and Kohlie, Rose and Lattwein,
                      Erik and Schmitz, Dietmar and Calabresi, Peter A and Pardo,
                      Carlos A and Prüss, Harald and Ruprecht, Klemens and
                      Benjamin Larman, H.},
      title        = {{S}pecific viral antibodies associate with anti-{NMDAR}
                      encephalitis after herpes simplex encephalitis.},
      journal      = {Brain, behavior and immunity},
      volume       = {130},
      issn         = {0889-1591},
      address      = {Orlando, Fla. [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-01042},
      pages        = {106073},
      year         = {2025},
      abstract     = {Herpes simplex encephalitis (HSE) patients may develop
                      secondary anti-N-methyl-D-aspartate receptor (NMDAR)
                      encephalitis (NMDARE), associated with worsened long-term
                      neurological outcome. Immunosuppressive treatment can limit
                      NMDAR autoantibody-mediated pathology, but early predictive
                      biomarkers for the risk of NMDARE are lacking. In a
                      multicenter study, we performed unbiased antibody reactome
                      profiling using Phage ImmunoPrecipitation Sequencing
                      (PhIP-Seq). HSE patients with secondary NMDARE (n = 13)
                      versus those without (n = 10) showed enhanced antibody
                      responses against HSV-1, but not HSV-2, which comprised
                      specific antibodies to five peptides of the HSV-1 UL42 and
                      UL48 proteins. A score of these signature CSF antibodies
                      identified HSE patients with secondary NMDARE with a
                      sensitivity of $75\%,$ a specificity of > $99\%,$ a positive
                      predictive value of $90\%,$ a negative predictive value of >
                      $97\%$ and an odds ratio (OR) of 209 (CI: 28 - 1,582) across
                      all individuals in this study, and with similar performance
                      values in serum $(>66\%,$ $>99\%,$ $>88\%,$ $>96\%,$ OR 307
                      (15 - 6,089)). These signature antibodies represent a
                      promising biomarker to identify HSE patients at risk for
                      NMDARE development. In NMDARE patients without a history of
                      HSE and in MS patients, no disease-associated HSV antibody
                      reactivity patterns were detected. Furthermore, we
                      introduced the Multiplexed Index Calculations of the
                      Antibody Reactome (MICAR) metric to characterize proteomic
                      targets of compartment-specific antibody responses, an
                      approach that is applicable in neuroimmunology and other
                      compartmentalized disease states.},
      keywords     = {Antibody reactome (Other) / Encephalitis (Other) / HSE
                      (Other) / HSV (Other) / Intrathecal synthesis (Other) /
                      MICAR (Other) / NMDAR (Other) / PhIP-Seq (Other)},
      cin          = {AG Prüß / AG Schmitz},
      ddc          = {150},
      cid          = {I:(DE-2719)1810003 / I:(DE-2719)1810004},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 351 -
                      Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40803454},
      doi          = {10.1016/j.bbi.2025.106073},
      url          = {https://pub.dzne.de/record/280960},
}