Home Increased serum concentrations of soluble ST2 are associated with pulmonary complications and mortality in polytraumatized patients
Article
Licensed
Unlicensed Requires Authentication

Increased serum concentrations of soluble ST2 are associated with pulmonary complications and mortality in polytraumatized patients

  • Thomas Haider , Elisabeth Simader , Philipp Hacker , Hendrik J. Ankersmit , Thomas Heinz , Stefan Hajdu and Lukas L. Negrin EMAIL logo
Published/Copyright: January 17, 2018

Abstract

Background:

We sought to evaluate the role of soluble ST2 (suppression of tumorigenicity) serum concentrations in polytraumatized patients and its potential role as biomarker for pulmonary complications.

Methods:

We included severely injured patients (injury severity score≥16) admitted to our level I trauma center and analyzed serum samples obtained on the day of admission and on day 2. Furthermore, patients with isolated thoracic injury and healthy probands were included and served as control groups. Serum samples were analyzed for soluble ST2 concentrations with a commercially available ELISA kit.

Results:

A total of 130 patients were included in the present study. Five patients with isolated thoracic injury and eight healthy probands were further included. Serum analyses revealed significantly elevated concentrations of soluble ST2 in polytraumatized patients compared to patients suffering from isolated thoracic trauma and healthy probands. In polytraumatized patients who developed pulmonary complications (acute respiratory distress syndrome and pneumonia) and in patients who died, significantly higher serum concentrations of soluble ST2 were found on day 2 (p<0.001). Serum concentrations of soluble ST2 on day 2 were of prognostic value to predict pulmonary complications in polytraumatized patients (area under the curve=0.720, 95% confidence interval=0.623–0.816). Concomitant thoracic trauma had no further impact on serum concentrations of soluble ST2.

Conclusions:

Serum concentrations of soluble ST2 are upregulated following polytrauma. Increased concentrations were associated with worse outcome.


Corresponding author: Lukas L. Negrin, MD, PhD, MSc, Department of Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

Acknowledgments

We would like to thank Claudia Gahleitner for her excellent support in statistics.

  1. Conflict of interest statement: The authors declare no potential conflict of interest associated with the present study.

  2. Author contributions: Design of the study: T.Ha. and L.L.N.; sample collection: L.L.N., S.H. and E.S.; conduction of experiments: T.Ha., E.S. and P.H.; preparation of the manuscript: T.Ha., T.H., H.J.A. and L.L.N.; proofreading: L.L.N., S.H., T.H. and H.J.A. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Research funding: None declared.

  4. Employment or leadership: None declared.

  5. Honorarium: None declared.

  6. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. WHO: Injuries and violence: the facts, 2014.Search in Google Scholar

2. Frohlich M, Lefering R, Probst C, Paffrath T, Schneider MM, Maegele M, et al. Epidemiology and risk factors of multiple-organ failure after multiple trauma: an analysis of 31,154 patients from the TraumaRegister DGU. J Trauma Acute Care Surg 2014;76:921–7; discussion 927–928.10.1097/TA.0000000000000199Search in Google Scholar PubMed

3. Lenz A, Franklin GA, Cheadle WG. Systemic inflammation after trauma. Injury 2007;38:1336–45.10.1016/j.injury.2007.10.003Search in Google Scholar PubMed

4. Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg 2012;72:1491–501.10.1097/TA.0b013e318256e000Search in Google Scholar PubMed PubMed Central

5. Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med 2008;29:617–25, viii.10.1016/j.ccm.2008.06.010Search in Google Scholar PubMed PubMed Central

6. Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 2010;10:103–10.10.1038/nri2692Search in Google Scholar PubMed

7. Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov 2008;7: 827–40.10.1038/nrd2660Search in Google Scholar PubMed PubMed Central

8. Mildner M, Storka A, Lichtenauer M, Mlitz V, Ghannadan M, Hoetzenecker K, et al. Primary sources and immunological prerequisites for sST2 secretion in humans. Cardiovasc Res 2010;87:769–77.10.1093/cvr/cvq104Search in Google Scholar PubMed

9. Shao D, Perros F, Caramori G, Meng C, Dormuller P, Chou PC, et al. Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension. Biochem Biophys Res Commun 2014;451:8–14.10.1016/j.bbrc.2014.06.111Search in Google Scholar PubMed

10. Beer L, Szerafin T, Mitterbauer A, Debreceni T, Maros T, Dworschak M, et al. Continued mechanical ventilation during coronary artery bypass graft operation attenuates the systemic immune response. Eur J Cardiothorac Surg 2013;44:282–7.10.1093/ejcts/ezs659Search in Google Scholar PubMed

11. Takezako N, Hayakawa M, Hayakawa H, Aoki S, Yanagisawa K, Endo H, et al. ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells. Biochem Biophys Res Commun 2006;341:425–32.10.1016/j.bbrc.2005.12.206Search in Google Scholar PubMed

12. Dieplinger B, Egger M, Koehler W, Firlinger F, Poelz W, Lenz K, et al. Prognostic value of soluble ST2 in an unselected cohort of patients admitted to an intensive care unit – The Linz Intensive Care Unit (LICU) study. Clin Chim Acta 2012;413: 587–93.10.1016/j.cca.2011.11.028Search in Google Scholar PubMed

13. Dieplinger B, Egger M, Leitner I, Firlinger F, Poelz W, Lenz K, et al. Interleukin 6, galectin 3, growth differentiation factor 15, and soluble ST2 for mortality prediction in critically ill patients. J Crit Care 2016;34:38–45.10.1016/j.jcrc.2016.03.020Search in Google Scholar PubMed

14. Mueller T, Dieplinger B, Gegenhuber A, Poelz W, Pacher R, Haltmayer M. Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem 2008;54:752–6.10.1373/clinchem.2007.096560Search in Google Scholar PubMed

15. Lichtenauer M, Jirak P, Wernly B, Paar V, Rohm I, Jung C, et al. A comparative analysis of novel cardiovascular biomarkers in patients with chronic heart failure. Eur J Intern Med 2017;44: 31–8.10.1016/j.ejim.2017.05.027Search in Google Scholar PubMed

16. Rensing H, Bauer M. [Multiple organ failure. Mechanisms, clinical manifestations and treatment strategies]. Anaesthesist 2001;50:819–41.10.1007/s001010100217Search in Google Scholar PubMed

17. Keel M, Trentz O. Pathophysiology of polytrauma. Injury 2005;36:691–709.10.1016/j.injury.2004.12.037Search in Google Scholar PubMed

18. Pape HC, Lefering R, Butcher N, Peitzman A, Leenen L, Marzi I, et al. The definition of polytrauma revisited: an international consensus process and proposal of the new ‘Berlin definition’. J Trauma Acute Care Surg 2014;77:780–6.10.1097/TA.0000000000000453Search in Google Scholar PubMed

19. Negrin LL, Halat G, Prosch H, Hupfl M, Hajdu S, Heinz T. Soluble receptor for advanced glycation end products quantifies lung injury in polytraumatized patients. Ann Thorac Surg 2017;103:1587–93.10.1016/j.athoracsur.2016.09.021Search in Google Scholar PubMed

20. Hildebrand F, Pape HC, Krettek C. [The importance of cytokines in the posttraumatic inflammatory reaction]. Unfallchirurg 2005;108:793–4, 796–803.10.1007/s00113-005-1005-1Search in Google Scholar PubMed

21. Pape HC, Tsukamoto T, Kobbe P, Tarkin I, Katsoulis S, Peitzman A. Assessment of the clinical course with inflammatory parameters. Injury 2007;38:1358–64.10.1016/j.injury.2007.09.026Search in Google Scholar PubMed

22. Tschoeke SK, Ertel W. Immunoparalysis after multiple trauma. Injury 2007;38:1346–57.10.1016/j.injury.2007.08.041Search in Google Scholar PubMed

23. Jenkins WS, Roger VL, Jaffe AS, Weston SA, AbouEzzeddine OF, Jiang R, et al. Prognostic value of soluble ST2 after myocardial infarction: a community perspective. Am J Med 2017;130:1112.e9–15.10.1016/j.amjmed.2017.02.034Search in Google Scholar PubMed PubMed Central

24. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon SD, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002;106:2961–6.10.1161/01.CIR.0000038705.69871.D9Search in Google Scholar PubMed PubMed Central

25. Bajwa EK, Volk JA, Christiani DC, Harris RS, Matthay MA, Thompson BT, et al. Prognostic and diagnostic value of plasma soluble suppression of tumorigenicity-2 concentrations in acute respiratory distress syndrome. Crit Care Med 2013;41:2521–31.10.1097/CCM.0b013e3182978f91Search in Google Scholar PubMed PubMed Central

26. Hoogerwerf JJ, Tanck MW, van Zoelen MA, Wittebole X, Laterre PF, van der Poll T. Soluble ST2 plasma concentrations predict mortality in severe sepsis. Intensive Care Med 2010;36:630–7.10.1007/s00134-010-1773-0Search in Google Scholar PubMed PubMed Central

27. Brunner M, Krenn C, Roth G, Moser B, Dworschak M, Jensen-Jarolim E, et al. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Intensive Care Med 2004;30:1468–73.10.1007/s00134-004-2184-xSearch in Google Scholar PubMed

28. Huber S, Biberthaler P, Delhey P, Trentzsch H, Winter H, van Griensven M, et al. Predictors of poor outcomes after significant chest trauma in multiply injured patients: a retrospective analysis from the German Trauma Registry (Trauma Register DGU(R)). Scand J Trauma Resusc Emerg Med 2014;22:52.10.1186/s13049-014-0052-4Search in Google Scholar PubMed PubMed Central

29. Ehrnthaller C, Flierl M, Perl M, Denk S, Unnewehr H, Ward PA, et al. The molecular fingerprint of lung inflammation after blunt chest trauma. Eur J Med Res 2015;20:70.10.1186/s40001-015-0164-ySearch in Google Scholar PubMed PubMed Central

30. Seitz DH, Perl M, Liener UC, Tauchmann B, Braumuller ST, Bruckner UB, et al. Inflammatory alterations in a novel combination model of blunt chest trauma and hemorrhagic shock. J Trauma 2011;70:189–96.10.1097/TA.0b013e3181d7693cSearch in Google Scholar PubMed

31. Ganie FA, Lone H, Lone GN, Wani ML, Singh S, Dar AM, et al. Lung contusion: a clinico-pathological entity with unpredictable clinical course. Bull Emerg Trauma 2013;1:7–16.Search in Google Scholar


Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0762).


Received: 2017-8-26
Accepted: 2017-11-14
Published Online: 2018-1-17
Published in Print: 2018-4-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Scientific publishing in the “predatory” era
  4. The influence of age and other biological variables on the estimation of reference limits of cardiac troponin T
  5. Reviews
  6. Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: a systematic review
  7. GSTP1 methylation in cancer: a liquid biopsy biomarker?
  8. Opinion Paper
  9. Practical recommendations for managing hemolyzed samples in clinical chemistry testing
  10. Genetics and Molecular Diagnostics
  11. Non-invasive prenatal diagnosis of paternally inherited disorders from maternal plasma: detection of NF1 and CFTR mutations using droplet digital PCR
  12. Circulating miR-21, miR-210 and miR-146a as potential biomarkers to differentiate acute tubular necrosis from hepatorenal syndrome in patients with liver cirrhosis: a pilot study
  13. Pleiotropy of ABO gene: correlation of rs644234 with E-selectin and lipid levels
  14. General Clinical Chemistry and Laboratory Medicine
  15. Three-year customer satisfaction survey in laboratory medicine in a Chinese university hospital
  16. Measurement of sirolimus concentrations in human blood using an automated electrochemiluminescence immunoassay (ECLIA): a multicenter evaluation
  17. Precision, accuracy, cross reactivity and comparability of serum indices measurement on Abbott Architect c8000, Beckman Coulter AU5800 and Roche Cobas 6000 c501 clinical chemistry analyzers
  18. Commutability of control materials for external quality assessment of serum apolipoprotein A-I measurement
  19. Development of a new biochip array for APOE4 classification from plasma samples using immunoassay-based methods
  20. Validation of a high-performance liquid chromatography method for thiopurine S-methyltransferase activity in whole blood using 6-mercaptopurine as substrate
  21. Increased serum concentrations of soluble ST2 are associated with pulmonary complications and mortality in polytraumatized patients
  22. Reference Values and Biological Variations
  23. Determination of age- and sex-specific 99th percentiles for high-sensitive troponin T from patients: an analytical imprecision- and partitioning-based approach
  24. Effect of preanalytical and analytical variables on the clinical utility of mean platelet volume
  25. Serum prolactin levels across pregnancy and the establishment of reference intervals
  26. Gender-partitioned patient medians of serum albumin requested by general practitioners for the assessment of analytical stability
  27. Cancer Diagnostics
  28. Detection of EGFR, KRAS and BRAF mutations in metastatic cells from cerebrospinal fluid
  29. Cardiovascular Diseases
  30. No additional value of conventional and high-sensitivity cardiac troponin over clinical scoring systems in the differential diagnosis of type 1 vs. type 2 myocardial infarction
  31. Letters to the Editor
  32. Rare inclusion bodies within monocytes at accelerated phase of Chediak-Higashi syndrome
  33. A specific abnormal scattergram of peripheral blood leukocytes that may suggest hairy cell leukemia
  34. Spuriously low lymphocyte count associated with pseudoerythroblastemia in a patient with chronic lymphocytic leukemia treated with ibrutinib
  35. Performance evaluation of a new automated fourth-generation HIV Ag/Ab combination chemiluminescence immunoassay
  36. False increase of glycated hemoglobin due to aspirin interference in Tosoh G8 analyzer
  37. Assessment of in vitro stability: a call for harmonization across studies
  38. Comparison between blood gas analyzer and central laboratory analyzer for the determination of electrolytes in patients with acute respiratory acidosis
Downloaded on 24.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2017-0762/html
Scroll to top button