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  1. Article ; Online: Emergence of antibodies endowed with proteolytic activity against High-mobility group box 1 protein (HMGB1) in patients surviving septic shock.

    Barnay-Verdier, Stéphanie / Borde, Chloé / Fattoum, Lakhdar / Wootla, Bharath / Lacroix-Desmazes, Sébastien / Kaveri, Srini / Gibot, Sébastien / Maréchal, Vincent

    Cellular immunology

    2019  Volume 347, Page(s) 104020

    Abstract: High-mobility group box 1 (HMGB1) concentration in serum or plasma has been proposed as an important biological marker in various inflammation-related pathologies. We previously showed that low titer autoantibodies against HMGB1 could emerge during the ... ...

    Abstract High-mobility group box 1 (HMGB1) concentration in serum or plasma has been proposed as an important biological marker in various inflammation-related pathologies. We previously showed that low titer autoantibodies against HMGB1 could emerge during the course of sepsis. Importantly their presence was positively related with patients' survival. In this study, we focused on plasma samples from 2 patients who survived sepsis and exhibited high titer antibodies to HMGB1. These antibodies were proved to be specific for HMGB1 since they did not bind to HMGB2 or to human serum albumin. Following IgG purification, it has shown that both patients secreted HMGB1-hydrolyzing autoantibodies in vitro. These findings suggested that proteolytic antibodies directed against HMGB1 can be produced in patients surviving septic shock.
    MeSH term(s) Autoantibodies/blood ; Autoantibodies/immunology ; HMGB1 Protein/immunology ; HMGB2 Protein/immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Proteolysis ; Serum Albumin, Human/immunology ; Shock, Septic/immunology ; Shock, Septic/mortality ; Shock, Septic/pathology
    Chemical Substances Autoantibodies ; HMGB1 Protein ; HMGB1 protein, human ; HMGB2 Protein ; Immunoglobulin G ; Serum Albumin, Human (ZIF514RVZR)
    Language English
    Publishing date 2019-11-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2019.104020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The effect of HMGB1, a damage-associated molecular pattern molecule, on polymorphonuclear neutrophil migration depends on its concentration.

    Berthelot, Florence / Fattoum, Lakhdar / Casulli, Sarah / Gozlan, Joël / Maréchal, Vincent / Elbim, Carole

    Journal of innate immunity

    2011  Volume 4, Issue 1, Page(s) 41–58

    Abstract: Polymorphonuclear neutrophils (PMN) play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in case of excessive or misdirected responses. Release of the alarmin high-mobility group box 1 (HMGB1) by ... ...

    Abstract Polymorphonuclear neutrophils (PMN) play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in case of excessive or misdirected responses. Release of the alarmin high-mobility group box 1 (HMGB1) by cells that die at an inflammatory site may act as an alert signal for the immune system. We studied the effect of HMGB1 on human PMN migration, using whole-blood samples to avoid cell activation associated with isolation procedures. HMGB1 50-100 ng/ml reduced baseline PMN migration as well as formyl-methionyl-leucyl-phenylalanine- and IL-8-induced PMN chemotaxis. This inhibitory effect was mediated by the RAGE receptor. In contrast, a higher HMGB1 concentration (5,000 ng/ml) had a chemoattractant effect on PMN through IL-8 production. This effect required the engagement of Toll-like receptors 2 and 4 in addition to the RAGE receptor. The A box component of HMGB1, which antagonizes the endogenous protein, reduced chemotaxis and also strongly inhibited the enhancement of PMN migration observed with the highest HMGB1 concentration. In contrast, the B box, reported to be the active form of HMGB1, exerted a chemoattractant effect. These results strongly point to a key regulatory role of HMGB1 in PMN recruitment to inflammatory tissues. The A box component could potentially serve to inhibit inappropriate PMN recruitment during chronic inflammatory disorders associated with excessive HMGB1 release.
    MeSH term(s) Chemotaxis, Leukocyte/drug effects ; Chemotaxis, Leukocyte/immunology ; Chronic Disease ; Dose-Response Relationship, Drug ; HMGB1 Protein/immunology ; HMGB1 Protein/pharmacology ; Humans ; Inflammation/immunology ; Interleukin-8/immunology ; Interleukin-8/pharmacology ; N-Formylmethionine Leucyl-Phenylalanine/immunology ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Neutrophils/immunology ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Toll-Like Receptor 2/immunology ; Toll-Like Receptor 4/immunology
    Chemical Substances CXCL8 protein, human ; HMGB1 Protein ; Interleukin-8 ; TLR2 protein, human ; TLR4 protein, human ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6)
    Language English
    Publishing date 2011-08-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2454158-8
    ISSN 1662-8128 ; 1662-811X
    ISSN (online) 1662-8128
    ISSN 1662-811X
    DOI 10.1159/000328798
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock.

    Barnay-Verdier, Stéphanie / Fattoum, Lakhdar / Borde, Chloé / Kaveri, Srini / Gibot, Sébastien / Maréchal, Vincent

    Intensive care medicine

    2011  Volume 37, Issue 6, Page(s) 957–962

    Abstract: Purpose: To assess the prevalence and predictive value of natural autoantibodies to high-mobility group box 1 (HMGB1) during sepsis.: Methods: Anti-HMGB1 and anti-human serum albumin (HSA) autoantibodies were detected by ELISA in 178 plasma samples ... ...

    Abstract Purpose: To assess the prevalence and predictive value of natural autoantibodies to high-mobility group box 1 (HMGB1) during sepsis.
    Methods: Anti-HMGB1 and anti-human serum albumin (HSA) autoantibodies were detected by ELISA in 178 plasma samples longitudinally collected from 40 critically ill patients with septic shock. One hundred thirty-two plasma samples from healthy donors were used as control.
    Results: IgGs to HMGB1 were detected in 15/40 patients (37.5%). The prevalence of anti-HMGB1 antibodies was significantly higher in the patients who survived (55%) compared to the patients who did not (20%) (p<0.0001). The detection of anti-HMGB1 antibodies during the course of the disease was significantly associated with patient survival (p=0.038). Moreover, there is a progressive and significant emergence of anti-HMGB1 antibodies during the course of the disease, mostly in patients who survived.
    Conclusions: This study shows that autoantibodies to HMGB1 are produced during sepsis and are associated with a favorable outcome in patients undergoing septic shock.
    MeSH term(s) Adult ; Aged ; Autoantibodies/blood ; Autoantibodies/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; France ; HMGB1 Protein/immunology ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Shock, Septic/physiopathology ; Survival
    Chemical Substances Autoantibodies ; HMGB1 Protein
    Language English
    Publishing date 2011-02-26
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-011-2192-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Effect of HMGB1, a Damage-Associated Molecular Pattern Molecule, on Polymorphonuclear Neutrophil Migration Depends on Its Concentration

    Berthelot, Florence / Fattoum, Lakhdar / Casulli, Sarah / Gozlan, Joël / Maréchal, Vincent / Elbim, Carole

    Journal of Innate Immunity

    2011  Volume 4, Issue 1, Page(s) 41–58

    Abstract: Polymorphonuclear neutrophils (PMN) play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in case of excessive or misdirected responses. Release of the alarmin high-mobility group box 1 (HMGB1) by ... ...

    Institution Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMR S 872 et Université Paris Descartes, UMR S 872, INSERM, Paris, France
    Abstract Polymorphonuclear neutrophils (PMN) play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in case of excessive or misdirected responses. Release of the alarmin high-mobility group box 1 (HMGB1) by cells that die at an inflammatory site may act as an alert signal for the immune system. We studied the effect of HMGB1 on human PMN migration, using whole-blood samples to avoid cell activation associated with isolation procedures. HMGB1 50–100 ng/ml reduced baseline PMN migration as well as formyl-methionyl-leucyl-phenylalanine- and IL-8-induced PMN chemotaxis. This inhibitory effect was mediated by the RAGE receptor. In contrast, a higher HMGB1 concentration (5,000 ng/ml) had a chemoattractant effect on PMN through IL-8 production. This effect required the engagement of Toll-like receptors 2 and 4 in addition to the RAGE receptor. The A box component of HMGB1, which antagonizes the endogenous protein, reduced chemotaxis and also strongly inhibited the enhancement of PMN migration observed with the highest HMGB1 concentration. In contrast, the B box, reported to be the active form of HMGB1, exerted a chemoattractant effect. These results strongly point to a key regulatory role of HMGB1 in PMN recruitment to inflammatory tissues. The A box component could potentially serve to inhibit inappropriate PMN recruitment during chronic inflammatory disorders associated with excessive HMGB1 release.
    Keywords Neutrophils ; Alarmine ; Chemotaxis ; Inflammation
    Language English
    Publishing date 2011-08-19
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Research Article
    ZDB-ID 2454158-8
    ISSN 1662-8128 ; 1662-811X
    ISSN (online) 1662-8128
    ISSN 1662-811X
    DOI 10.1159/000328798
    Database Karger publisher's database

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  5. Article ; Online: A differential concentration-dependent effect of IVIg on neutrophil functions: relevance for anti-microbial and anti-inflammatory mechanisms.

    Casulli, Sarah / Topçu, Selma / Fattoum, Lakhdar / von Gunten, Stephan / Simon, Hans-Uwe / Teillaud, Jean-Luc / Bayry, Jagadeesh / Kaveri, Srini V / Elbim, Carole

    PloS one

    2011  Volume 6, Issue 10, Page(s) e26469

    Abstract: Background: Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) ...

    Abstract Background: Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders.
    Methodology/principal findings: We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation.
    Conclusions/significance: IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent.
    MeSH term(s) Anti-Infective Agents/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Apoptosis/drug effects ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Humans ; Immunoglobulins, Intravenous/pharmacology ; Lipopolysaccharides/pharmacology ; Neutrophil Activation/drug effects ; Neutrophils/cytology ; Neutrophils/drug effects ; Neutrophils/metabolism
    Chemical Substances Anti-Infective Agents ; Anti-Inflammatory Agents ; Immunoglobulins, Intravenous ; Lipopolysaccharides
    Language English
    Publishing date 2011-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0026469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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