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Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGARCIA, GEOFFREY
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorLABROUCHE-COLOMER, Sylvie
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUVIGNAUD, Alexandre
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorCLEQUIN, Etienne
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDUSSIAU, Charles
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMALVY, Denis
ORCID: 0000-0003-1948-9355
IDREF: 148480993
dc.contributor.authorPREVEL, Renaud
dc.contributor.authorZOUINE, Atika
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorPELLEGRIN, Isabelle
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorGORET, Julien
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorMAMANI-MATSUDA, Maria
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorDEWITTE, Antoine
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJAMES, Chloe
dc.date.accessioned2024-05-03T08:56:31Z
dc.date.available2024-05-03T08:56:31Z
dc.date.issued2024-03-07
dc.identifier.issn1479-5876en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/199596
dc.description.abstractEnBackgroundThrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19.MethodsBiological samples were obtained from hospitalized patients (15 severe, 37 critical at sampling) and 93 non-severe ambulatory cases. Our aims were to compare NET biomarkers, functional DNase levels, and explore mechanisms driving any imbalance concerning disease severity.ResultsFunctional DNase levels were diminished in the most severe patients, paralleling an imbalance between NET markers and DNase activity. DNase1 antigen levels were higher in ambulatory cases but lower in severe patients. DNase1L3 antigen levels remained consistent across subgroups, not rising alongside NET markers. DNASE1 polymorphisms correlated with reduced DNase1 antigen levels. Moreover, a quantitative deficiency in plasmacytoid dendritic cells (pDCs), which primarily express DNase1L3, was observed in critical patients. Analysis of public single-cell RNAseq data revealed reduced DNase1L3 expression in pDCs from severe COVID-19 patient.ConclusionSevere and critical COVID-19 cases exhibited an imbalance between NET and DNase functional activity and quantity. Early identification of NETosis imbalance could guide targeted therapies against thrombo-inflammation in COVID-19-related sepsis, such as DNase administration, to avert clinical deterioration.Trial registration: COVERAGE trial (NCT04356495) and COLCOV19-BX study (NCT04332016).ConclusionSevere and critical COVID-19 cases exhibited an imbalance between NET and DNase functional activity and quantity. Early identification of NETosis imbalance could guide targeted therapies against thrombo-inflammation in COVID-19-related sepsis, such as DNase administration, to avert clinical deterioration.Trial registration: COVERAGE trial (NCT04356495) and COLCOV19-BX study (NCT04332016).
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enImpaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease
dc.title.alternativeJ Transl Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1186/s12967-024-05044-7en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38454482en_US
bordeaux.journalJournal of Translational Medicineen_US
bordeaux.page246en_US
bordeaux.volume22en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionCNRS
bordeaux.teamGHIGS_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDInstitut de Recherche pour le Développementen_US
hal.identifierhal-04567306
hal.version1
hal.date.transferred2024-05-03T08:56:34Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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