Accuracy of circulating histones in predicting persistent organ failure and mortality in patients with acute pancreatitis

Liu, T; Huang, Wei; Szatmary, Peter; Abrams, Simon T.; Alhamdi, Yasir; Lin, Ziqi; Greenhalf, William; Wang, G; Sutton, Robert; Toh, Cheng Hock

doi:10.1002/bjs.10538

Cited by 62 publications

(45 citation statements)

References 37 publications

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“…Histones have been examined in experimental AP murine models, and most have shown a correlation between circulating levels and AP severity [188,189]. Histones are essential for DNA packaging and genetic regulation.…”

Section: Histonesmentioning

confidence: 99%

Multifactorial Scores and Biomarkers of Prognosis of Acute Pancreatitis: Applications to Research and Practice

Silva-Vaz

Abrantes

Castelo‐Branco

et al. 2020

IJMS

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Acute pancreatitis (AP) is a severe inflammation of the pancreas presented with sudden onset and severe abdominal pain with a high morbidity and mortality rate, if accompanied by severe local and systemic complications. Numerous studies have been published about the pathogenesis of AP; however, the precise mechanism behind this pathology remains unclear. Extensive research conducted over the last decades has demonstrated that the first 24 h after symptom onset are critical for the identification of patients who are at risk of developing complications or death. The identification of these subgroups of patients is crucial in order to start an aggressive approach to prevent mortality. In this sense and to avoid unnecessary overtreatment, thereby reducing the financial implications, the proper identification of mild disease is also important and necessary. A large number of multifactorial scoring systems and biochemical markers are described to predict the severity. Despite recent progress in understanding the pathophysiology of AP, more research is needed to enable a faster and more accurate prediction of severe AP. This review provides an overview of the available multifactorial scoring systems and biochemical markers for predicting severe AP with a special focus on their advantages and limitations.

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Section: Histonesmentioning

confidence: 99%

Multifactorial Scores and Biomarkers of Prognosis of Acute Pancreatitis: Applications to Research and Practice

Silva-Vaz

Abrantes

Castelo‐Branco

et al. 2020

IJMS

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“…Extracellular histones H3 and H4 (but not H1 or H2A/H2B) also activate vascular endothelial cells to increase cell surface expression of E‐selectin, ICAM‐1 and VCAM‐1, thereby increasing leukocyte adhesion, rolling and transmigration in a TLR9‐dependent manner 24. In higher concentrations, these histones are toxic to the endothelium and represent a putative mechanism for pulmonary haemorrhage and ARDS in sepsis13 or pancreatitis 25. Histones acting on endothelial cells via TLRs 2 and 4 also activate NF‐kB and AP‐1 pathways to induce tissue factor expression,26 thereby creating a pro‐thrombotic milieu contributing to the microvascular thrombosis seen in many acute inflammatory diseases.…”

Section: Histones As Dampsmentioning

confidence: 99%

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

Szatmary

Huang

Criddle

et al. 2018

J Cellular Molecular Medi

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Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.

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“…Histone H2A levels were significantly increased in plasma in AP. The quantitative assessment of histones in plasma has been demonstrated to accurately predict persistent organ failure and mortality in AP (55). Thus, the HBPs exhibiting the greatest fold change (Table 1) differences between the biological conditions.…”

Section: Discussionmentioning

confidence: 99%

The heparin-binding proteome in normal pancreas and murine experimental acute pancreatitis

Nunes

Brownridge

et al. 2018

Preprint

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QMN) ¶ These authors contributed equally to this work. Abstract Acute pancreatitis (AP) is acute inflammation of the pancreas, mainly caused by gallstones and alcohol, driven by changes in communication between cells. Heparin-binding proteins (HBPs) play a central role in health and diseases. Therefore, we used heparin affinity proteomics to identify extracellular HBPs in pancreas and plasma of normal mice and in a caerulein mouse model of AP. Many new extracellular HBPs (360) were discovered in the pancreas, taking the total number of HBPs known to 786. Extracellular pancreas HBPs form highly interconnected protein-protein interaction networks in both normal pancreas (NP) and AP. Thus, HBPs represent an important set of extracellular proteins with significant regulatory potential in the pancreas. HBPs in NP are associated with biological functions such as molecular transport and cellular movement that underlie pancreatic homeostasis. However, in AP HBPs are associated with additional inflammatory processes such as acute phase response signalling, complement activation and mitochondrial dysfunction, which has a central role in the development of AP. Plasma HBPs in AP included known AP biomarkers such as serum amyloid A, as well as emerging targets such as histone H2A. Other HBPs such as alpha 2-HS glycoprotein (AHSG) and histidine-rich glycoprotein (HRG) need further investigation for potential applications in the management of AP. Pancreas HBPs are extracellular and so easily accessible and are potential drug targets in AP, whereas plasma HBPs represent potential biomarkers for AP. Thus, their identification paves the way to determine which HBPs may have potential applications in the management of AP.

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Accuracy of circulating histones in predicting persistent organ failure and mortality in patients with acute pancreatitis

Cited by 62 publications

References 37 publications

Multifactorial Scores and Biomarkers of Prognosis of Acute Pancreatitis: Applications to Research and Practice

Multifactorial Scores and Biomarkers of Prognosis of Acute Pancreatitis: Applications to Research and Practice

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

The heparin-binding proteome in normal pancreas and murine experimental acute pancreatitis

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