Association of high mobility group box-1 protein levels with sepsis and outcome of severely burned patients

Huang, Lifeng; Yao, Yong‐Ming; Dong, Ning; Yu, Yan; He, Li-xin; Zhang, Sheng

doi:10.1016/j.cyto.2010.09.010

Cited by 38 publications

(31 citation statements)

References 40 publications

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“…In our cohort, survival without transplant was similar to that reported by others [29]. Baseline data for all biomarker observations in the healthy volunteer cohort were also comparable to published data [28, 30]. In APAP overdose patients with an abnormal liver function test (APAP-abnormal LFT) we positively identified the presence of both apoptosis and necrosis-related K18 and total HMGB1 by ELISA.…”

Section: Resultssupporting

confidence: 89%

RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity

Antoine

Jenkins

Dear

et al. 2012

Journal of Hepatology

301

349

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Background & Aims Full length keratin-18 (FL-K18) and High Mobility Group Box-1 (HMGB1) represent circulating indicators of necrosis during acetaminophen (APAP) hepatotoxicity in vivo. In addition, the caspase-cleaved fragment of K18 (cK18) and hyper-acetylated HMGB1 represent serum indicators of apoptosis and immune cell activation respectively. The study aim was to assess their mechanistic utility to establish the balance between apoptosis, necrosis and immune cell activation throughout the time course of clinical APAP hepatotoxicity. Methods HMGB1 (total, acetylated) and K18 (apoptotic, necrotic) were identified and quantified by novel LC-MS/MS assays in APAP overdose patients (n=78). Results HMGB1 (total; 15.4±1.9ng/ml, p<0.01, acetylated; 5.4±2.6ng/ml, p<0.001), cK18 (5649.8±721.0U/l, p<0.01) and FL-K18 (54770.2±6717.0U/l, p<0.005) were elevated in the sera of APAP overdose patients with liver injury compared to overdose patients without liver injury and healthy volunteers. HMGB1 and FL-K18 correlated with alanine aminotransferase (ALT) activity (R2=0.60 and 0.58 respectively, p<0.0001) and prothrombin time (R2=0.62 and 0.71 respectively, p<0.0001). Increased total and acetylated HMGB1 and FL-K18 were associated with worse prognosis (King’s College Criteria) or patients that died/required liver transplant compared to spontaneous survivors (all p<0.05-0.001), a finding not reflected by ALT and supported by ROC analysis. Acetylated HMGB1 was a better predictor of outcome than the other markers of cell death. Conclusion K18 and HMGB1 represent blood-based tools to investigate the cell death balance clinical APAP hepatotoxicity. Activation of the immune response was seen later in the time course as shown by the distinct profile of acetylated HMGB1 and was associated with worse outcome.

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Section: Resultssupporting

confidence: 89%

RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity

Antoine

Jenkins

Dear

et al. 2012

Journal of Hepatology

301

349

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“…High-mobility group box 1 levels are increased in patients with community-acquired pneumonia (14), severe burns (15, 16), sepsis (17), or pancreatitis (18). Recently, we reported that persistent HMGB1 elevation after CLP is sufficient to induce immune dysregulation (splenomegaly, leukocytosis, and splenocyte priming) lasting for at least 8 weeks after onset of sepsis (8).…”

Section: Discussionmentioning

confidence: 99%

High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors

Valdés‐Ferrer

Rosas-Ballina

Olofsson

et al. 2013

Shock

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Severe sepsis is a life-threatening complication of infection and injury affecting more than 700,000 people in the United States each year. Two thirds of patients with severe sepsis will survive to be discharged. Survivors have high incidence of cognitive impairment, immune dysregulation, functional impairments with marked disability, and 5-year mortality rates of 82%. High-mobility group box 1 (HMGB1) is necessary and sufficient mediator of sepsis pathogenesis in experimental models of this syndrome. The spleen is a crucial organ in the immune response to severe infection, and splenocyte dysfunction occurs in sepsis survivors. We hypothesized that HMGB1 plays a key role in mediating the immune dysfunction of splenocytes in sepsis survivors. Mice that survived cecal ligation and puncture–induced sepsis develop persistent splenomegaly; furthermore, splenocytes derived from sepsis survivors had enhanced responses to lipopolysaccharide ex vivo. Administration of neutralizing anti-HMGB1 antibody to sepsis survivors attenuated development of splenomegaly and reversed splenocyte priming. Splenocytes exposed to HMGB1 and subsequently challenged with cognate ligands to Toll-like receptor 2 (TLR2,) TLR4, TLR9, and RAGE (receptor for advanced glycation end product) receptors had enhanced cytokine release as compared with splenocytes not previously exposed to HMGB1. Exposure of TLR2−/−, TLR9−/−, or RAGE−/− splenocytes to HMGB1 enhanced responses to other TLR receptor ligands; in contrast, HMGB1 failed to prime TLR4−/− splenocytes. These findings indicate that exposure to HMGB1 enhances splenocyte responses to secondary inflammatory challenges, a priming effect dependent on TLR4, and that anti-HMGB1 monoclonal antibody may be beneficial in sepsis survivors.

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“…Severe skin thermal injury breaks the balance of the immune system which plays an important and complex role in the whole pathophysiologic process [2,3]. There are strong dependencies between mortality, morbidity and immune system imbalance [4].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammative effect of glycyrrhizin on rat thermal injury via inhibition of high-mobility group box 1 protein

Shen

Cui

Lin

et al. 2015

Burns

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Association of high mobility group box-1 protein levels with sepsis and outcome of severely burned patients

Cited by 38 publications

References 40 publications

RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity

RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity

High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors

Anti-inflammative effect of glycyrrhizin on rat thermal injury via inhibition of high-mobility group box 1 protein

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