Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7704
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dc.contributor.authorHollerbach, Anne-
dc.contributor.authorMüller-Calleja, Nadine-
dc.contributor.authorPedrosa, Denise-
dc.contributor.authorCanisius, Antje-
dc.contributor.authorSprinzl, Martin F.-
dc.contributor.authorFalter, Tanja-
dc.contributor.authorRossmann, Heidi-
dc.contributor.authorBodenstein, Marc-
dc.contributor.authorWerner, Christian-
dc.contributor.authorSagoschen, Ingo-
dc.contributor.authorMünzel, Thomas-
dc.contributor.authorSchreiner, Oliver-
dc.contributor.authorSivanathan, Visvakanth-
dc.contributor.authorReuter, Michael-
dc.contributor.authorNiermann, Johannes-
dc.contributor.authorGalle, Peter R.-
dc.contributor.authorTeyton, Luc-
dc.contributor.authorRuf, Wolfram-
dc.contributor.authorLackner, Karl J.-
dc.date.accessioned2022-09-12T08:24:15Z-
dc.date.available2022-09-12T08:24:15Z-
dc.date.issued2021-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7719-
dc.description.abstractBackground Coronavirus disease 19 (COVID-19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID-19 patients, but their association with the clinical course of COVID-19 remains unproven. Objectives To analyze the presence and relevance of lipid-binding aPL in hospitalized COVID-19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR-proven severe acute respiratory syndrome–coronavirus 2 infection were analyzed for the presence of aPL and clinical severity of COVID-19. Results We here demonstrate that lipid-binding aPL are common in COVID-19. COVID-19 patients with lipid-binding aPL have higher median concentrations of C-reactive protein and D-dimer, and are more likely to have a critical clinical course and fatal outcome. Lipid-binding aPL isolated from COVID-19 patients target the recently described cell surface complex of lysobisphosphatidic acid (LBPA) with the protein C receptor (EPCR) to induce prothrombotic and inflammatory responses in monocytes and endothelial cells. We show that B1a cells producing lipid-reactive aPL of the IgG isotype circulate in the blood of COVID-19 patients. In vivo, COVID-19 aPL accelerate thrombus formation in an experimental mouse model dependent on the recently delineated signaling pathway involving EPCR-LBPA. Conclusions COVID-19 patients rapidly expand B1a cells secreting pathogenic lipid-binding aPL with broad thrombotic and inflammatory effects. The association with markers of inflammation and coagulation, clinical severity, and mortality suggests a causal role of aPL in COVID-19–associated coagulopathy.en_GB
dc.language.isoengde
dc.rightsCC BY-NC*
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titlePathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19en_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7704-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleJournal of thrombosis and haemostasisde
jgu.journal.volume19de
jgu.journal.issue9de
jgu.pages.start2335de
jgu.pages.end2347de
jgu.publisher.year2021-
jgu.publisher.nameWiley-Blackwellde
jgu.publisher.placeOxfordde
jgu.publisher.issn1538-7836de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1111/jth.15455de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:JGU-Publikationen

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