Journal Article DZNE-2025-01042

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Specific viral antibodies associate with anti-NMDAR encephalitis after herpes simplex encephalitis.

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2025
Elsevier Orlando, Fla. [u.a.]

Brain, behavior and immunity 130, 106073 () [10.1016/j.bbi.2025.106073]

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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.

Keyword(s): Antibody reactome ; Encephalitis ; HSE ; HSV ; Intrathecal synthesis ; MICAR ; NMDAR ; PhIP-Seq

Classification:

Contributing Institute(s):
  1. Autoimmune Encephalopathies (AG Prüß)
  2. Network Dysfunction (AG Schmitz)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
  2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > B DZNE > B DZNE-AG Schmitz
Institute Collections > B DZNE > B DZNE-AG Prüß
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 Record created 2025-09-03, last modified 2025-09-18