Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock

Barnay‐Verdier, Stéphanie; Fattoum, Lakhdar; Borde, Chloé; Kaveri, Srini V.; Gibot, Sébastien; Maréchal, Vincent

doi:10.1007/s00134-011-2192-6

Cited by 51 publications

(45 citation statements)

References 22 publications

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“…Although HMGB1 was initially described as a nuclear protein with important regulatory functions associated with gene expression (1), more recent studies have shown that HMGB1 has potent proinflammatory actions and can be classified as a danger-associated molecular pattern mediator. Although therapeutic approaches aimed at blocking cellular release of HMGB1 or inhibiting the actions of extracellular HMGB1 are of benefit in diminishing tissue injury and organ dysfunction in acute and chronic inflammatory conditions, such as hemorrhage, sepsis, and rheumatoid arthritis, there is also reason to believe that HMGB1 plays a beneficial role in microbial eradication, not only through its proinflammatory actions, but also by modulating neutrophil chemotaxis (1,4,5,20,39). Our present findings, showing that HMGB1 can potentiate NET formation, suggest a novel mechanism by which HMGB1 may enhance host defense to bacterial infection and contribute to inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

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HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4

Tadié

Bae

Jiang³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

289

205

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Although neutrophil extracellular traps (NETs) form to prevent dissemination of pathogenic microorganisms, excessive release of DNA and DNA-associated proteins can also perpetuate sterile inflammation. In this study, we found that the danger-associated molecular pattern protein high-mobility group box 1 (HMGB1) can induce NET formation. NET formation was found after exposure of wild-type and receptor for advanced glycation end products-deficient neutrophil to HMGB1, whereas deficiency of Toll-like receptor (TLR)4 diminished the ability of neutrophils to produce NETs. Incubation of neutrophils with HMGB1 significantly increased the amount of DNA and histone 3 released as well as intracellular histone 3 citrullination, a signaling event that precedes chromatin decondensation. In vivo, neutrophils isolated from bronchoalveolar lavages of mice exposed to LPS and HMGB1 showed consistently greater ability to produce NETs compared with pulmonary neutrophils from mice that received LPS alone. In contrast, mice treated with LPS and neutralizing antibody to HMGB1 had decreased amounts of the inflammatory cytokines TNF-α and macrophage inflammatory protein 2, as well as of free DNA and histone 3 in bronchoalveolar lavage fluids. Airway neutrophils from LPS-exposed mice that had been treated with anti-HMGB1 antibodies showed decreased citrullination of histone 3. These results demonstrate that interactions between HMGB1 and TLR4 enhance the formation of NETs and provide a novel mechanism through which HMGB1 may contribute to the severity of neutrophil-associated inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

“…Plasma and tissue levels of HMGB1 are elevated in acute inflammatory conditions, such as during severe infection, burns, hemorrhage, and lung injury (1,4,20). Increased circulating concentrations of HMGB1 are also associated with chronic inflammatory disorders, including rheumatoid arthritis and systemic lupus erythematosus.…”

mentioning

confidence: 99%

HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4

Tadié

Bae

Jiang³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

289

205

View full text Add to dashboard Cite

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“…antioxidants, anti-inflammatory agents) [15][16][17][18] into improved outcomes of critically ill patients. This issue has gradually been overcome with mandatory antioxidant vaccination programs [19] and the correction of mitochondrial damage on location by emergency medical services [20], allowing intensive care medicine to focus on supportive care rather than late "metabolic and immune damage control".…”

Section: "Prediction Is Very Difficult Especially About the Future" mentioning

confidence: 99%

Visit to intensive care of 2050

2016

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“…Erh ö hte HMGB1-Konzentrationen finden sich zudem im Blut bei erregerbedingter Sepsis, vor allem bei Patienten mit schlechter Prognose [83] , wohingegen das Auftreten von Auto-Antik ö rpern mit einem besseren Krankheitsverlauf assoziiert ist und eine protektive Funktion zu haben scheint [166] .…”

Section: Klinische Relevanz Immunogener Zelltodmarker Als Biomarker Bunclassified

Immunogene Zelltodmarker HMGB1 und sRAGE als neue prädiktive und prognostische Serum Biomarker bei Tumorerkrankungen/Immunogenic cell death markers HMGB1 and sRAGE as new predictive and prognostic serum biomarkers in cancer disease

Wittwer¹,

Holdenrieder²

2013

Laboratoriumsmedizin

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ZusammenfassungImmunogene Zelltodmarker sind eine inhomogene Gruppe von Molekülen, die während Zelltodprozessen wie Apoptose, Nekrose oder weiteren Formen freigesetzt werden. Je nach Zusammensetzung des extrazellulären Milieus können diese „Danger associated molecular patterns“ (DAMPs) wie das „High mobility group box 1“ (HMGB1) Protein das Immunsystem stimulierend oder inhibierend beeinflussen. Bei Tumorerkrankungen scheint eine kontinuierliche Freisetzung von HMGB1, u.a. über eine Vermittlung durch den zellulären Bindungspartner „Receptor of advanced glycation end products“ (RAGE), zu einer Förderung des Tumorwachstums zu führen, während die pulsatile Freisetzung während zytotoxischer Therapie zu einer verbesserten antitumorösen Immunantwort beitragen könnte. Lösliches RAGE (sRAGE) kann hingegen die Effekte von extrazellulärem HMGB1 abpuffern. In diesem Review werden die strukturellen und funktionalen Charakteristika dieser immunogenen Zelltodmarker sowie ihre Rolle in der Pathophysiologie von nicht-malignen und malignen Erkrankungen vorgestellt; sodann wird ihre Relevanz als Serum-Biomarker für die Diagnose, die Prognoseabschätzung, die Prädiktion und das Monitoring des Ansprechens einer zytotoxischen Therapie bei Tumorpatienten beleuchtet. Bei Patienten mit verschiedenen Tumorerkrankungen wurden im Vergleich zu gesunden Personen erhöhte Serumkonzentrationen von HMGB1 und niedrigere sRAGE-Werte gefunden. Zudem waren hohe HMGB1- und niedrige sRAGE-Serumwerte vor und während einer zytotoxischen Therapie mit einem unzureichenden Ansprechen auf die Behandlung und einem kürzeren Überleben assoziiert. Diese Ergebnisse weisen die immunogenen Zelltodmarker HMGB1 und sRAGE als neue, vielversprechende Biomarker zur Abschätzung der Prognose, Stratifikation der Patienten und zum Therapiemonitoring bei Tumorpatienten aus.

show abstract

Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock

Abstract: This study shows that autoantibodies to HMGB1 are produced during sepsis and are associated with a favorable outcome in patients undergoing septic shock.

Cited by 51 publications

References 22 publications

HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4

HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4

Visit to intensive care of 2050

Immunogene Zelltodmarker HMGB1 und sRAGE als neue prädiktive und prognostische Serum Biomarker bei Tumorerkrankungen/Immunogenic cell death markers HMGB1 and sRAGE as new predictive and prognostic serum biomarkers in cancer disease

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