Markus Bauswein, Saida Zoubaa, Martina Toelge, Lisa Eidenschink, Markus J Riemenschneider, Bernhard Neumann, De-Hyung Lee, Ehab Eid, Dennis Tappe, Hans Helmut Niller, André Gessner, Barbara Schmidt, Sigrid Bülow, Klemens Angstwurm
{"title":"Long-term elevation of complement factors in cerebrospinal fluid of patients with Borna disease virus 1 (BoDV-1) encephalitis","authors":"Markus Bauswein, Saida Zoubaa, Martina Toelge, Lisa Eidenschink, Markus J Riemenschneider, Bernhard Neumann, De-Hyung Lee, Ehab Eid, Dennis Tappe, Hans Helmut Niller, André Gessner, Barbara Schmidt, Sigrid Bülow, Klemens Angstwurm","doi":"10.1093/infdis/jiae183","DOIUrl":null,"url":null,"abstract":"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 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 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 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.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Infectious Diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/infdis/jiae183","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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 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 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 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.