The significance of sTREM-1 as a diagnostic biomarker of sepsis in the context of Sepsis-3 definition
1Clinic for Infectious Diseases, University of Novi Sad, Faculty of Medicine, Clinical Center of Vojvodina, Novi Sad, Serbia
2 Department of Anesthesia and Reanimation, University of Novi Sad, Faculty of Medicine, Clinical Centre of Vojvodina, Clinical Center of Vojvodina, Emergency Center, Novi Sad, Serbia
3 University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
4 Department of Ear, Nose and Throat Diseases, University of Novi Sad, Faculty of Medicine, Clinical Centre of Vojvodina, Novi Sad, Serbia
DOI: 10.22514/SV141.042018.11 Vol.14,Issue 1,March 2018 pp.65-70
Published: 27 March 2018
Aim. Sepsis remains the leading cause of mortality in spite of advanced diagnostics. The aim of the study was to test the diag-nostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the context of a new definition of sepsis. Methods. The study was conducted on 41 patients who were suspected of having sep-sis according to SIRS (Systemic Inflamma-tory Response Syndrome) criteria or sterile SIRS. 20 healthy volunteer blood donors were the control group (adult patients of both sexes). According to the latest sepsis criteria (Sepsis-3), patients were retrospec-tively divided into three subgroups: septic patients, patients with SIRS plus infection and patients with sterile SIRS (non-infec-tious SIRS).
All subjects had concentrations of sTREM-1 determined by the ELISA meth-od (Abcam commercial test, Cambridge, MA, USA). Samples were collected upon admission to hospital and kept at -20°C until laboratory analysis was performed. Results. Concentrations of sTREM-1 were significantly increased in patients, com-pared to the healthy population (p=0.021), but there were no significant differences among subgroups of patients (SIRS plus infection vs. sepsis p=0.871, SIRS plus in-fection vs. sterile SIRS p=0.72, sepsis vs. sterile SIRS p=0.65).
The value of 300pg/mL was determined to be the optimal cut-off. Concentrations of sTREM-1 were significantly higher in septic patients who did not develop Multiple Organ Dysfunction Syndrome (MODS) within the first 48 hours after admission than in those who did.
Conclusion. According to our results, sTREM-1 failed to express significance as a diagnostic biomarker of sepsis, according to the new definition. Also, it seems not to be a valuable marker in differentiation of sepsis and non-infective SIRS.
sepsis, sTREM-1, SIRS
VEDRANA PETRIC,SNEZANA BRKIC,DAJANA LENDAK,DUNJA MIHAJLOVIC,ALEKSANDRA NOVAKOV MIKIC,SNEZANA BRKIC,SLOBODANKA LEMAJIC KOMAZEC. The significance of sTREM-1 as a diagnostic biomarker of sepsis in the context of Sepsis-3 definition. Signa Vitae. 2018. 14(1);65-70.
1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med 2013;41:580–637.
2. Singer M, SC Deutschman, Seymour WC, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Defini-tions for Sepsis and Septic Shock -3. JAMA 2016;315:801-10.
3. Breslow MJ, Badawi O. Severity scoring in the critically ill: Part 1 - Interpretation and accuracy of outcome prediction scoring sys-tems. Chest 2012;141:245–52.
4. Soreng K, Levy HR. Procalcitonin: an Emerging Biomarker of Bacterial Sepsis. Clin Microbiol Newsl 2011;33:171–8.
5. Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, et al. The use of maximum SOFA score to quantify organ dysfunc-tion/failure in intensive care. Results of a prospective, multicentre study. Intensive Care Med 1999;25:686-96.
6. Vodnik JT. Značaj preoperativnog i postoperativnog određivanja biomarkera sepse za dijagnozu i prognozu intraabdominalnih in-fekcija. Doktorska disertacija. Srbija: Univerzitet u Beogradu, Farmaceutski fakultet Beograd; 2014.
7. Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care 2010;14:R15.
8. Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 2000;164:4991–5.
9. Prüfer S, Weber M, Sasca D, Teschner D, Wölfel C, Stein P, et al. Distinct signaling cascades of TREM-1, TLR and NLR in neutrophils and monocytic cells. J Innate Immun 2013;6:339–52.
10. 1Netea MG, Azam T, Ferwerda G, Girardin SE, Kim SH, Dinarello CA. Triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies the signals induced by the NACHTLRR(NLR) pattern recognition receptors. J Leukocyte Biol 2006;80:1454–61.
11. Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001;410:1103–7.
12. Ford JW, McVicar DW. TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol 2009;21:38–46.
13. Dunne, WM. Laboratory Diagnosis of Sepsis? No SIRS, Not Just Yet. J Clin Microbiol 2015;8:2404–9.
14. Singer M. The role of mitochondrial dysfunction in sepsis-induced multi-organ failure. Virulence 2014;5:66-72.
15. Johnson CD, Abu-Hilal M, Members of the British Acute Pancreatitis Study Group. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut 2004;53:1340–4.
16. Ogawa M. Acute pancreatitis and cytokines: 'second attack' by septic complication leads to organ failure. Pancreas 1998;3:312–5.
17. Lundberg AH, Granger DN, Russell J, Sabek O, Henry J, Gaber L, et al. Quantitative measurement of P- and E-selectin adhesion molecules in acute pancreatitis: correlation with distant organ injury. Ann Surg 2000;231:213–22.
18. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003;29(4):530–8.
19. Kenzaka T, Okayama M, Kuroki S, Fukui M, Yahata S, Hayashi H, et al. Importance of vital signs to the early diagnosis and se-verity of sepsis: association between vital signs and sequential organ failure assessment score in patients with sepsis. Intern Med 2012;51:871–6.
20. Bayram H, Tünger Ö, Çivi M, Yüceyar MH, Ulman C, Horasan DD, Çetin ÇB. Diagnostic and prognostic value of procalcitonin and sTREM-1 levels in sepsis. Turk J Med Sci 2015;45:578-86.
21. Suberviola B, Castellanos-Ortega A, González-Castro A, García-Astudillo LA, Fernández-Miret B. Prognostic value of procalcitonin,
C- reactive protein and leukocytes in septic shock. Med Intensiva (English Ed) 2012;36:177–84.
22. Endo S, Aikawa N, Fujishima S, Sekine I, Kogawa K, Yamamoto Y, et al. Usefulness of procalcitonin serum level for the discrimina-tion of severe sepsis from sepsis: a multicenter prospective study. J Infect Chemother 2008;14:244–9.
23. Wu Y, Wa ng F, Fan X, Bao R, Bo L, Li J, Deng X . Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory pa-tients: a systematic review and meta-analysis. Crit Care 2012;16:R229.
24. Samaraj R, Zingarelli B, Wong RH. Role of Biomarkers in Sepsis Care. Shock 2013;40:5.
25. Gibot S, Cravoisy A, Kolpp-Sarada MN, Bene M, Faure G, Bollaert PE, et al. Time-course of sTREM (soluble triggering receptor ex-pressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis. Crit Care Med 2005;33:792-6.
26. Jiyong J, Tiancha H, Wei C, Huahao S. Diagnostic value of the soluble triggering receptor expressed on myeloid cells-1 in bacterial infection: a meta-analysis. Intensive Care Med 2009;35:587-95.
27. Danai P, Martin SG. Epidemiology of sepsis: Recent advances. Curr Infect Dis Rep 2005;7(5):329-34.
28. Gibot S, Béné MC, Noel R, Massin F, Guy J, Cravoisy A, et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med 2012;186:65-71.
29. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, Larsen K. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care 2007;11:R38.
30. Barati M, Bashar FR, Shahrami R, Zadeh MH, Taher MT, Nojomi M. Soluble triggering receptor expressed on myeloid cells 1 and the diagnosis of sepsis. J Crit Care 2010;25:362.
31. Latour-Pérez J, Alcalá-López A, García-García MA, Sánchez-Hernández JF, Abad-Terrado C, Viedma-Contreras JA, et al. Diagnostic accuracy of sTREM-1 to identify infection in critically ill patients with systemic inflammatory response syndrome. Clin Biochem 2010;43:720-4.
32. Su L, Feng L, Song Q, Kang H, Zhang X, Liang Z, et al. Diagnostic Value of Dynamics Serum sCD163, sTREM-1, PCT, and CRP in Differentiating Sepsis, Severity Assessment, and Prognostic Prediction. Mediat Inflamm 2013;2013:9.
33. Ferat-Osorio E, Esquivel-Callejas N, Wong-Baeza I, Aduna-Vicente R, Arriaga-Pizano L, Sanchez-Fernandez P, et al. The increased expression of TREM-1 on monocytes is associated with infectious and noninfectious inflammatory processes. JSR 2008;150(1):110–7.
34. Su L, Feng L, Song Q, Kang H, Zhang X, Liang Z, et al. Diagnostic Value of Dynamics Serum sCD163, sTREM-1, PCT, and CRP in Differentiating Sepsis, Severity Assessment, and Prognostic Prediction. Mediat Inflamm 2013;2013:9.
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