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

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...

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Autori principali: Kreye, Jakob (Autore) , Morgenlander, William R. (Autore) , Thakar, Manjusha (Autore) , Schulte-Frankenfeld, Poul (Autore) , Schott, Sarah (Autore) , Bünger, Isabel (Autore) , Kornau, Hans-Christian (Autore) , Angkeow, Julia W. (Autore) , Jayaraman, Sahana (Autore) , Otto, Carolin (Autore) , Hahn, Wiebke (Autore) , Lewerenz, Jan (Autore) , Thaler, Franziska S. (Autore) , Korporal-Kuhnke, Mirjam (Autore) , Melzer, Nico (Autore) , Dargvainiene, Justina (Autore) , Bien, Christian G. (Autore) , Kohlie, Rose (Autore) , Lattwein, Erik (Autore) , Schmitz, Dietmar (Autore) , Calabresi, Peter A. (Autore) , Pardo, Carlos A. (Autore) , Prüß, Harald (Autore) , Ruprecht, Klemens (Autore) , Larman, Benjamin H. (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: November 2025
In: Brain, behavior and immunity
Year: 2025, Volume: 130, Pages: 1-14
ISSN:1090-2139
DOI:10.1016/j.bbi.2025.106073
Accesso online:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1016/j.bbi.2025.106073
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0889159125003083
Testo
Note sull'autore:Jakob Kreye, William R. Morgenlander, Manjusha Thakar, Poul M. Schulte-Frankenfeld, Sarah Schott, Isabel Bünger, Hans-Christian Kornau, Julia W. Angkeow, Sahana Jayaraman, Carolin Otto, Wiebke Hahn, Jan Lewerenz, Franziska S. Thaler, Mirjam Korporal-Kuhnke, Nico Melzer, Justina Dargvainiene, Christian G. Bien, Rose Kohlie, Erik Lattwein, Dietmar Schmitz, Peter A. Calabresi, Carlos A. Pardo, Harald Prüss, Klemens Ruprecht, H. Benjamin Larman
Descrizione
Riassunto: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.
Descrizione del documento:Online veröffentlicht am: 11. August 2025
Gesehen am 28.05.2026
Descrizione fisica:Online Resource
ISSN:1090-2139
DOI:10.1016/j.bbi.2025.106073

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