Journal Article

DZNE-2025-01042

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Specific viral antibodies associate with anti-NMDAR encephalitis after herpes simplex encephalitis.

Kreye, J. (First author)DZNE* ; Morgenlander, W. R. ; Thakar, M. ; Schulte-Frankenfeld, P. M. ; Schott, S. ; Bünger, I. ; Kornau, H.-C.DZNE* ; Angkeow, J. W. ; Jayaraman, S. ; Otto, C. ; Hahn, W. ; Lewerenz, J. ; Thaler, F. S. ; Korporal-Kuhnke, M. ; Melzer, N. ; Dargvainiene, J. ; Bien, C. G. ; Kohlie, R. ; Lattwein, E. ; Schmitz, D.DZNE* ; Calabresi, P. A. ; Pardo, C. A. ; Prüss, H.DZNE* ; Ruprecht, K. ; Benjamin Larman, H.

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

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Please use a persistent id in citations: doi:10.1016/j.bbi.2025.106073

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): Humans (MeSH) ; Encephalitis, Herpes Simplex: immunology (MeSH) ; Encephalitis, Herpes Simplex: complications (MeSH) ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis: immunology (MeSH) ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis: etiology (MeSH) ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis: virology (MeSH) ; Female (MeSH) ; Male (MeSH) ; Antibodies, Viral: blood (MeSH) ; Antibodies, Viral: immunology (MeSH) ; Antibodies, Viral: cerebrospinal fluid (MeSH) ; Adult (MeSH) ; Middle Aged (MeSH) ; Herpesvirus 2, Human: immunology (MeSH) ; Herpesvirus 1, Human: immunology (MeSH) ; Autoantibodies (MeSH) ; Biomarkers: blood (MeSH) ; Young Adult (MeSH) ; Receptors, N-Methyl-D-Aspartate: immunology (MeSH) ; Antibody reactome ; Encephalitis ; HSE ; HSV ; Intrathecal synthesis ; MICAR ; NMDAR ; PhIP-Seq

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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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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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