Inflammasome proteins as biomarkers of traumatic brain injury

Background: The inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We ha...

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Autores: Kerr, Nadine, Lee, Stephanie W, Pérez-Bárcena, Jon, Crespí, Catalina, Ibáñez Domínguez, Javier Angel, Bullock, M. Ross, Dietrich, W. Dalton, Keane, Robert W, Vaccari, Juan Pablo de Rivero
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/22612
Acceso en línea:https://hdl.handle.net/20.500.12105/22612
Access Level:acceso abierto
Palabra clave:Biomarcadores
Femenino
Interleucina-18
Masculino
Inflamasomas
Caspasa 1
Proteínas Adaptadoras de Señalización CARD
Humanos
Persona de Mediana Edad
Lesiones Traumáticas del Encéfalo
Anciano
Anciano de 80 o más Años
Adulto
Interleucina-1beta
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/22612
network_acronym_str ES
network_name_str España
repository_id_str
spelling Inflammasome proteins as biomarkers of traumatic brain injuryKerr, NadineLee, Stephanie WPérez-Bárcena, JonCrespí, CatalinaIbáñez Domínguez, Javier AngelBullock, M. RossDietrich, W. DaltonKeane, Robert WVaccari, Juan Pablo de RiveroBiomarcadoresFemeninoInterleucina-18MasculinoInflamasomasCaspasa 1Proteínas Adaptadoras de Señalización CARDHumanosPersona de Mediana EdadLesiones Traumáticas del EncéfaloAncianoAnciano de 80 o más AñosAdultoInterleucina-1betaBackground: The inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with TBI and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels. Methods and findings: Here we extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18. Analysis was carried out using the Ella Simple Plex system (Protein Simple) to determine the sensitivity and specificity of inflammasome proteins as biomarkers of TBI. Receiver operator characteristic (ROC) curves, confidence intervals and likelihood ratios for each biomarker was determined. ROC curves, confidence intervals, sensitivity and specificity for each biomarker examined revealed that caspase-1 (0.93 area under the curve (AUC)) and ASC (0.90 AUC) in serum and ASC (1.0 AUC) and IL-18 (0.84 AUC) in CSF are promising biomarkers of TBI pathology. Importantly, higher protein levels (above 547.6 pg/ml) of ASC (0.91 AUC) were consistent with poorer outcomes after TBI as determined by the Glasgow Outcome Scale-Extended (GOSE). Conclusion: These findings indicate that inflammasome proteins are excellent diagnostic and predictive biomarkers of TBI.Public Library of Science (PLOS)20242024-09-0620182018-12-3120182018-12-31research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttps://hdl.handle.net/20.500.12105/22612reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/226122026-06-12T12:43:37Z
dc.title.none.fl_str_mv Inflammasome proteins as biomarkers of traumatic brain injury
title Inflammasome proteins as biomarkers of traumatic brain injury
spellingShingle Inflammasome proteins as biomarkers of traumatic brain injury
Kerr, Nadine
Biomarcadores
Femenino
Interleucina-18
Masculino
Inflamasomas
Caspasa 1
Proteínas Adaptadoras de Señalización CARD
Humanos
Persona de Mediana Edad
Lesiones Traumáticas del Encéfalo
Anciano
Anciano de 80 o más Años
Adulto
Interleucina-1beta
title_short Inflammasome proteins as biomarkers of traumatic brain injury
title_full Inflammasome proteins as biomarkers of traumatic brain injury
title_fullStr Inflammasome proteins as biomarkers of traumatic brain injury
title_full_unstemmed Inflammasome proteins as biomarkers of traumatic brain injury
title_sort Inflammasome proteins as biomarkers of traumatic brain injury
dc.creator.none.fl_str_mv Kerr, Nadine
Lee, Stephanie W
Pérez-Bárcena, Jon
Crespí, Catalina
Ibáñez Domínguez, Javier Angel
Bullock, M. Ross
Dietrich, W. Dalton
Keane, Robert W
Vaccari, Juan Pablo de Rivero
author Kerr, Nadine
author_facet Kerr, Nadine
Lee, Stephanie W
Pérez-Bárcena, Jon
Crespí, Catalina
Ibáñez Domínguez, Javier Angel
Bullock, M. Ross
Dietrich, W. Dalton
Keane, Robert W
Vaccari, Juan Pablo de Rivero
author_role author
author2 Lee, Stephanie W
Pérez-Bárcena, Jon
Crespí, Catalina
Ibáñez Domínguez, Javier Angel
Bullock, M. Ross
Dietrich, W. Dalton
Keane, Robert W
Vaccari, Juan Pablo de Rivero
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Biomarcadores
Femenino
Interleucina-18
Masculino
Inflamasomas
Caspasa 1
Proteínas Adaptadoras de Señalización CARD
Humanos
Persona de Mediana Edad
Lesiones Traumáticas del Encéfalo
Anciano
Anciano de 80 o más Años
Adulto
Interleucina-1beta
topic Biomarcadores
Femenino
Interleucina-18
Masculino
Inflamasomas
Caspasa 1
Proteínas Adaptadoras de Señalización CARD
Humanos
Persona de Mediana Edad
Lesiones Traumáticas del Encéfalo
Anciano
Anciano de 80 o más Años
Adulto
Interleucina-1beta
description Background: The inflammasome plays an important role in the inflammatory innate immune response after central nervous system (CNS) injury. Inhibition of the inflammasome after traumatic brain injury (TBI) results in improved outcomes by lowering the levels of caspase-1 and interleukin (IL)-1b. We have previously shown that inflammasome proteins are elevated in the cerebrospinal fluid (CSF) of patients with TBI and that higher levels of these proteins were consistent with poorer outcomes after TBI when compared to patients that presented these inflammasome proteins at lower levels. Methods and findings: Here we extend our work by analyzing serum from 21 TBI patients and CSF from 18 TBI patients compared to 120 serum samples and 30 CSF samples from no-TBI donor controls for the expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin(IL)-1b and IL-18. Analysis was carried out using the Ella Simple Plex system (Protein Simple) to determine the sensitivity and specificity of inflammasome proteins as biomarkers of TBI. Receiver operator characteristic (ROC) curves, confidence intervals and likelihood ratios for each biomarker was determined. ROC curves, confidence intervals, sensitivity and specificity for each biomarker examined revealed that caspase-1 (0.93 area under the curve (AUC)) and ASC (0.90 AUC) in serum and ASC (1.0 AUC) and IL-18 (0.84 AUC) in CSF are promising biomarkers of TBI pathology. Importantly, higher protein levels (above 547.6 pg/ml) of ASC (0.91 AUC) were consistent with poorer outcomes after TBI as determined by the Glasgow Outcome Scale-Extended (GOSE). Conclusion: These findings indicate that inflammasome proteins are excellent diagnostic and predictive biomarkers of TBI.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-12-31
2018
2018-12-31
2024
2024-09-06
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/22612
url https://hdl.handle.net/20.500.12105/22612
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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