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2021-12-01Zeitschriftenartikel
A Genetic Variation of Lipopolysaccharide Binding Protein Affects the Inflammatory Response and Is Associated with Improved Outcome during Sepsis
dc.contributor.authorKumpf, Oliver
dc.contributor.authorGürtler, Kathleen
dc.contributor.authorSur, Saubashya
dc.contributor.authorParvin, Monalisa
dc.contributor.authorZerbe, Lena-Karoline
dc.contributor.authorEckert, Jana K.
dc.contributor.authorWeber, Alexander N. R.
dc.contributor.authorOh, Djin-Ye
dc.contributor.authorLundvall, Linn
dc.contributor.authorHamann, Lutz
dc.contributor.authorSchumann, Ralf R.
dc.date.accessioned2024-07-10T09:00:11Z
dc.date.available2024-07-10T09:00:11Z
dc.date.issued2021-12-01none
dc.identifier.other10.4049/immunohorizons.2100095
dc.identifier.urihttp://edoc.rki.de/176904/11773
dc.description.abstractLPS binding protein (LBP) is an important innate sensor of microbial cell wall structures. Frequent functionally relevant mutations exist and have been linked to influence susceptibility to and course of bacterial infections. We examined functional properties of a single nucleotide polymorphism resulting in an exchange of phenylalanine to leucine at position 436 of LBP (rs2232618) and compared the frequent variant of the molecule with the rare one in ligand binding experiments. We then stimulated RAW cells with bacterial ligands in the presence of serum obtained from individuals with different LBP genotypes. We, furthermore, determined the potential effects of structural changes in the molecule by in silico modeling. Finally, we analyzed 363 surgical patients for this genetic variant and examined incidence and course of sepsis following surgery. We found that binding of LBP to bacterial ligands was reduced, and stimulation of RAW cells resulted in an increased release of TNF when adding serum from individuals carrying the F436L variant as compared with normal LBP. In silico analysis revealed structural changes of LBP, potentially explaining some of the effects observed for the LBP variant. Finally, patients carrying the F436L variant were found to be similarly susceptible for sepsis. However, we observed a more favorable course of severe infections in this cohort. Our findings reveal new insights into LPS recognition and the subsequent activation of the innate immune system brought about by LBP. The identification of a genetic variant of LBP influencing the course of sepsis may help to stratify individuals at risk and thus reduce clinical complications of patients.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY-NC-ND 3.0 DE) Namensnennung - Nicht-kommerziell - Keine Bearbeitung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/de/
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleA Genetic Variation of Lipopolysaccharide Binding Protein Affects the Inflammatory Response and Is Associated with Improved Outcome during Sepsisnone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/11773-7
dc.type.versionpublishedVersionnone
local.edoc.container-titleImmunoHorizonsnone
local.edoc.container-issn2573-7732none
local.edoc.pages12none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://journals.aai.org/immunohorizonsnone
local.edoc.container-publisher-nameThe American Association of Immunologists, Inc.none
local.edoc.container-volume5none
local.edoc.container-issue12none
local.edoc.container-reportyear2021none
dc.description.versionPeer Reviewednone

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