Long-term elevation of complement factors in cerebrospinal fluid of patients with Borna disease virus 1 (BoDV-1) encephalitis.

Borna disease virus 1 (BoDV-1) cerebrospinal fluid (CSF) complement system immunopathogenesis zoonosis

Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
09 Apr 2024
Historique:
received: 11 01 2024
revised: 26 03 2024
accepted: 04 04 2024
medline: 9 4 2024
pubmed: 9 4 2024
entrez: 9 4 2024
Statut: aheadofprint

Résumé

Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as severe encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and central nervous viral infections is increasing and specific inhibitors are available as therapeutic options. In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to non-inflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using post-mortem brain tissue samples. We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent and C3 complement deposits were detected in post-mortem brain sections. Intrathecal complement levels were negatively correlated with survival. Further investigations are warranted to clarify, whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis.

Sections du résumé

BACKGROUND BACKGROUND
Borna disease virus 1 (BoDV-1) causes rare but severe zoonotic infections in humans, presenting as severe encephalitis. The case-fatality risk is very high and no effective countermeasures have been established so far. An immunopathology is presumed, while data on immune responses in humans are limited. Evidence of a role of the complement system in various neurological disorders and central nervous viral infections is increasing and specific inhibitors are available as therapeutic options.
METHODS METHODS
In this study, we investigated factors of the complement system in the cerebrospinal fluid (CSF) of patients with BoDV-1 infections (n = 17) in comparison to non-inflammatory control CSF samples (n = 11), using a bead-based multiplex assay. In addition, immunohistochemistry was performed using post-mortem brain tissue samples.
RESULTS RESULTS
We found an intrathecal elevation of complement factors of all complement pathways and an active cascade during human BoDV-1 infections. The increase of certain complement factors such as C1q was persistent and C3 complement deposits were detected in post-mortem brain sections. Intrathecal complement levels were negatively correlated with survival.
CONCLUSION CONCLUSIONS
Further investigations are warranted to clarify, whether targeting the complement cascade by specific inhibitors might be beneficial for patients suffering from severe BoDV-1 encephalitis.

Identifiants

pubmed: 38591239
pii: 7642456
doi: 10.1093/infdis/jiae183
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Auteurs

Markus Bauswein (M)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.

Saida Zoubaa (S)

Department of Neuropathology, University Hospital Regensburg, 93053 Regensburg, Germany.

Martina Toelge (M)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.

Lisa Eidenschink (L)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.

Markus J Riemenschneider (MJ)

Department of Neuropathology, University Hospital Regensburg, 93053 Regensburg, Germany.

Bernhard Neumann (B)

Department of Neurology, Donau-Isar-Klinikum Deggendorf, 94469 Deggendorf, Germany.
Department of Neurology, University of Regensburg, Bezirksklinikum, 93053 Regensburg, Germany.

De-Hyung Lee (DH)

Department of Neurology, University of Regensburg, Bezirksklinikum, 93053 Regensburg, Germany.

Ehab Eid (E)

Department of Neurology, University of Regensburg, Bezirksklinikum, 93053 Regensburg, Germany.

Dennis Tappe (D)

Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Hans Helmut Niller (HH)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

André Gessner (A)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.
Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Barbara Schmidt (B)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.
Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Sigrid Bülow (S)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.

Klemens Angstwurm (K)

Department of Neurology, University of Regensburg, Bezirksklinikum, 93053 Regensburg, Germany.

Classifications MeSH