Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christof / Zettl, Uwe K.


IMPACT FACTOR 2018: 0.389

CiteScore 2018: 0.22

SCImago Journal Rank (SJR) 2018: 0.156
Source Normalized Impact per Paper (SNIP) 2018: 0.089

Print + Online
See all formats and pricing
More options …
Volume 40, Issue 3

Issues

HMGB1, nucleosomes and sRAGE as new prognostic serum markers after multiple trauma

Juliane Barbara Stahl / Eduard F. Hoecherl / Jürgen Durner / Dorothea Nagel / Konrad Wolf / Stefan Holdenrieder
  • Corresponding author
  • Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Sigmund-Freud Str. 15, 53127 Bonn, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-06-06 | DOI: https://doi.org/10.1515/labmed-2016-0004

Abstract

Background: The prognostic relevance of blood markers in multiple trauma is still a matter of controversial debate. Besides clinical scores new biomarkers indicating the disease severity and the prognosis during the first hours of therapy are highly needed to improve individual patient management.

Methods: In prospectively collected sera of 164 patients, among them 115 with multiple trauma, the values of circulating nucleosomes, high-mobility-group-box protein 1 (HMGB1) and soluble receptor of advanced glycation end products (sRAGE) were determined at time of admission to the resuscitation room. Disease severity and clinical status were quantified by injury severity score (ISS) and Glasgow Coma Scale (GCS). As controls, 24 patients with femoral neck fractures and 25 patients with ankle fractures (AFs) were included.

Results: Patients with severe multiple trauma (SMT) showed significantly higher HMGB1 and sRAGE levels than patients with moderate trauma and single fractures. Interestingly, HMGB1 and nucleosomes (R=0.56; p<0.01) as well as HMGB1 and sRAGE (R=0.44; p<0.01) correlated significantly with each other. In multiple trauma patients, high HMGB1 and sRAGE levels were significantly associated with more severe trauma according ISS (both p<0.01) and more severe traumatic brain injury (TBI) (GCS≤8; both p<0.01). Thirteen of the multiple injured patients died during the first week after trauma. Non-surviving patients showed significantly higher values of HMGB1, nucleosomes, and sRAGE than survivors (p<0.01; p=0.01; p=0.02). Best prediction of first-week mortality was obtained in receiver operating characteristic (ROC) curves for HMGB1 that yielded an area under the curve (AUC) of 90.6%.

Conclusions: HMGB1, nucleosomes and sRAGE are valuable biomarkers indicating trauma severity and prognosis of trauma patients.

Reviewed publication

FraunbergerP.

Keywords: HMGB1; nucleosomes; prognosis; serum biomarkers; sRAGE; trauma

References

  • 1.

    Heron M. Deaths: leading causes for 2007. Natl Vital Stat Rep 2011;59:1–95.Google Scholar

  • 2.

    Weber U, Ertel W. Introduction to the topic: the golden hour is decisive. Standard procedures in polytrauma. Orthopade 2005;34:821–2.Google Scholar

  • 3.

    Keel M, Trentz O. Pathophysiology of polytrauma. Injury 2005;36:691–709.Google Scholar

  • 4.

    Dewar D, Moore FA, Moore EE, Balogh Z. Postinjury multiple organ failure. Injury 2009;40:912–8.Google Scholar

  • 5.

    Khorasanizadeh S. The nucleosome: from genomic organization to genomic regulation. Cell 2004;116:259–72.Google Scholar

  • 6.

    Holdenrieder S, Stieber P. Clinical use of circulating nucleosomes. Crit Rev Clin Lab Sci 2009;46:1–24.Google Scholar

  • 7.

    Lo YM, Rainer TH, Chan LY, Hjelm NM, Cocks RA. Plasma DNA as a prognostic marker in trauma patients. Clin Chem 2000;46:319–23.Google Scholar

  • 8.

    Margraf S, Logters T, Reipen J, Altrichter J, Scholz M, Windolf J. Neutrophil-derived circulating free DNA (cf-DNA/NETs): a potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis. Shock 2008;30:352–8.Web of ScienceGoogle Scholar

  • 9.

    Geiger S, Holdenrieder S, Stieber P, Hamann GF, Bruening R, Ma J, et al. Nucleosomes as a new prognostic marker in early cerebral stroke. J Neurol 2007;254:617–23.Web of ScienceGoogle Scholar

  • 10.

    Martins GA, Kawamura MT, Carvalho Mda G. Detection of DNA in the plasma of septic patients. Ann NY Acad Sci 2000;906:134–40.Google Scholar

  • 11.

    Goodwin GH, Sanders C, Johns EW. A new group of chromatin-associated proteins with a high content of acidic and basic amino-acids. Eur J Biochem 1973;38:14–9.Google Scholar

  • 12.

    Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002;418:191–5.Web of ScienceGoogle Scholar

  • 13.

    Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007;81:1–5.Google Scholar

  • 14.

    Peltz ED, Moore EE, Eckels PC, Damle SS, Tsuruta Y, Johnson JL, et al. HMGB1 is markedly elevated within 6 hours of mechanical trauma in humans. Shock 2009;32:17–22.Web of ScienceGoogle Scholar

  • 15.

    Cohen MJ, Brohi K, Calfee CS, Rahn P, Chesebro BB, Christiaans SC, et al. Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion. Crit Care 2009;13:R174.Web of ScienceGoogle Scholar

  • 16.

    Rouhiainen A, Kuja-Panula J, Wilkman E, Pakkanen J, Stenfors J, Tuominen RK, et al. Regulation of monocyte migration by amphoterin (HMGB1). Blood 2004;104:1174–82.Google Scholar

  • 17.

    Abraham E. Unraveling the role of high mobility group box protein 1 in severe trauma. Crit Care 2009;13:1004.Google Scholar

  • 18.

    Stoetzer O, Wittwer C, Lehner J, Fahmueller Y, Kohles N, Fersching DM, et al. Circulating nucleosomes and biomarkers of immunogenic cell death as predictive and prognostic markers in cancer patients undergoing cytotoxic therapy. Expert Opin Biol Ther 2012;12(Suppl 1):S217–24.Web of ScienceGoogle Scholar

  • 19.

    Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 2005;83:876–86.Google Scholar

  • 20.

    Muhammad S, Barakat W, Stoyanov S, Murikinati S, Yang H, Tracey KJ, et al. The HMGB1 receptor RAGE mediates ischemic brain damage. J Neurosci 2008;28:12023–31.Google Scholar

  • 21.

    Geroldi D, Falcone C, Emanuele E. Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target. Curr Med Chem 2006;13:1971–8.Google Scholar

  • 22.

    Holdenrieder S, Stieber P, Bodenmuller H, Fertig G, Furst H, Schmeller N, et al. Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med 2001;39:596–605.Google Scholar

  • 23.

    Wittwer C, Lehner J, Fersching D, Siegele B, Stötzer O, Holdenrieder S. Methodical and preanalytical of a RAGE immunoassay. Anticancer Res 2012;32:2075–8.Google Scholar

  • 24.

    Lehner J, Wittwer C, Fersching D, Siegele B, Holdenrieder S, Stoetzer OJ. Methodical and preanalytical evaluation of an HMGB1 immunoassay. Anticancer Res 2012;32:2059–62.Google Scholar

  • 25.

    Gennarelli TA. The abbreviated injury scale. 1990 revision. Des Plaines, IL: Association for the Advancement of Automotive Medicine, 1990.Google Scholar

  • 26.

    Zuercher M, Ummenhofer W, Baltussen A, Walder B. The use of Glasgow Coma Scale in injury assessment: a critical review. Brain Inj 2009;23:371–84.Web of ScienceGoogle Scholar

  • 27.

    Probst C, Pape HC, Hildebrand F, Regel G, Mahlke L, Giannoudis P, et al. 30 years of polytrauma care: an analysis of the change in strategies and results of 4849 cases treated at a single institution. Injury 2009;40:77–83.Web of ScienceGoogle Scholar

  • 28.

    Kohles N, Nagel D, Jungst D, Durner J, Stieber P, Holdenrieder S. Prognostic relevance of oncological serum biomarkers in liver cancer patients undergoing transarterial chemoembolization therapy. Tumour Biol 2012;33:33–40.Google Scholar

  • 29.

    Beiter T, Fragasso A, Hudemann J, Niess AM, Simon P. Short-term treadmill running as a model for studying cell-free DNA kinetics in vivo. Clin Chem 2011;57:633–6.Web of ScienceGoogle Scholar

  • 30.

    Fahmueller YN, Nagel D, Hoffmann RT, Tatsch K, Jakobs T, Stieber P, et al. Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients. Int J Cancer 2013;132:2349–58.Web of ScienceGoogle Scholar

  • 31.

    Yang H, Ochani M, Li JH, Qiang XL, Tanovic M, Harris HE, et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 2004;101:296–301.Google Scholar

  • 32.

    Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed) 2010;2:1184–95.Google Scholar

  • 33.

    Bopp C, Hofer S, Weitz J, Bierhaus A, Nawroth PP, Martin E, et al. sRAGE is elevated in septic patients and associated with patients outcome. J Surg Res 2008;147:79–83.Web of ScienceGoogle Scholar

  • 34.

    Chawda MN, Hildebrand F, Pape HC, Giannoudis PV. Predicting outcome after multiple trauma: which scoring system? Injury 2004;35:347–58.Google Scholar

About the article

Correspondence: Stefan Holdenrieder, MD, Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Sigmund-Freud Str. 15, 53127 Bonn, Germany, Tel.: +49–228–287 12126, Fax: +49–228–287 12159, E-Mail:

aKonrad Wolf and Stefan Holdenrieder contributed equally to this work.


Received: 2016-01-07

Accepted: 2016-02-26

Published Online: 2016-06-06

Published in Print: 2016-06-01

Published in Print: 2016-06-01


Citation Information: LaboratoriumsMedizin, Volume 40, Issue 3, Pages 165–173, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2016-0004.

Export Citation

©2016 by De Gruyter.Get Permission

Comments (0)

Please log in or register to comment.
Log in