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Host Response Biomarkers in Sepsis: Overview on sTREM-1 Detection

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Sepsis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1237))

Abstract

The diagnosis of sepsis, and especially its differentiation from sterile inflammation, may be challenging. TREM-1, the triggering receptor expressed on myeloid cells-1, is an amplifier of the innate immune response. Its soluble form acts as a decoy for the natural TREM-1 ligand and dampens its activation. In this chapter, we review the numerous studies that have evaluated the usefulness of sTREM-1 concentration determination for the diagnosis and the prognosis evaluation of sepsis or localized infection. Nowadays, sandwich ELISA kits are available and the assay is described.

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References

  1. Tang BM, Eslick GD, Craig JC, McLean AS (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7:210–217

    Article  PubMed  CAS  Google Scholar 

  2. Atkinson AJ, Colburn WA, DeGruttola VG et al (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Article  Google Scholar 

  3. Marshall JC, Reinhart K (2009) Biomarkers of sepsis. Crit Care Med 37:2290–2298

    Article  PubMed  CAS  Google Scholar 

  4. Ford JW, McVicar DW (2009) TREM and TREM-like receptors in inflammation and disease. Curr Opin Immunol 21:38–46

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Hara H, Ishihara C, Takeuchi A et al (2007) The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat Immunol 8:619–629

    Article  PubMed  CAS  Google Scholar 

  6. Tessarz AS, Cerwenka A (2008) The TREM-1/DAP12 pathway. Immunol Lett 116:111–116

    Article  PubMed  CAS  Google Scholar 

  7. Dower K, Ellis DK, Saraf K et al (2008) Innate immune responses to TREM-1 activation: overlap, divergence, and positive and negative cross-talk with bacterial lipopolysaccharide. J Immunol 180:3520–3534

    Article  PubMed  CAS  Google Scholar 

  8. Bouchon A, Dietrich J, Colonna M (2000) Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 164:4991–4995

    Article  PubMed  CAS  Google Scholar 

  9. Bleharski JR, Kiessler V, Buonsanti C et al (2003) A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol 170:3812

    Article  PubMed  CAS  Google Scholar 

  10. Bouchon A, Facchetti F, Weigand MA, Colonna M (2001) TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 410:1103–1107

    Article  PubMed  CAS  Google Scholar 

  11. Gibot S, Kolopp-Sarda M-N, Béné M-C et al (2004) A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis. J Exp Med 200:1419–1426

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Lanier LL, Bakker AB (2000) The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol Today 21:611–614

    Article  PubMed  CAS  Google Scholar 

  13. Gómez-Piña V, Soares-Schanoski A, Rodríguez-Rojas A et al (2007) Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes. J Immunol 179:4065–4073

    Article  PubMed  Google Scholar 

  14. Wong-Baeza I, Gonz’alez-Rold’an N, Ferat-Osorio E et al (2006) Triggering receptor expressed on myeloid cells (TREM-1) is regulated post-transcriptionally and its ligand is present in the sera of some septic patients. Clin Exp Immunol 145:448–455

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Haselmayer P, Grosse-Hovest L, von Landenberg P et al (2007) TREM-1 ligand expression on platelets enhances neutrophil activation. Blood 110:1029–1035

    Article  PubMed  CAS  Google Scholar 

  16. Hamerman JA, Tchao NK, Lowell CA, Lanier LL (2005) Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat Immunol 6:579–586

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Hamerman JA, Jarjoura JR, Humphrey MB et al (2006) Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol 177:2051–2055

    Article  PubMed  CAS  Google Scholar 

  18. Gibot S, Cravoisy A, Levy B et al (2004) Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med 350:451–458

    Article  PubMed  CAS  Google Scholar 

  19. Gibot S, Kolopp-Sarda MN, Béné MC et al (2004) Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis. Ann Intern Med 141:9–15

    Article  PubMed  CAS  Google Scholar 

  20. Wang H, Chen B (2011) Diagnostic role of soluble triggering receptor expressed on myeloid cell-1 in patients with sepsis. World J Emerg Med 2:190–194

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Su L, Han B, Liu C et al (2012) Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study. BMC Infect Dis 12:157

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Latour-Pérez J, Alcalá-López A, García-García MÁ et al (2010) Diagnostic accuracy of sTREM-1 to identify infection in critically ill patients with systemic inflammatory response syndrome. Clin Biochem 43:720–724

    Article  PubMed  Google Scholar 

  23. Barati M, Bashar FR, Shahrami R et al (2010) Soluble triggering receptor expressed on myeloid cells 1 and the diagnosis of sepsis. J Crit Care 25:362.e1–362.e6

    Article  CAS  Google Scholar 

  24. Kofoed K, Andersen O, Kronborg G et al (2007) 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 11:R38

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chen H, Hung C, Tseng H, Yang R (2008) Soluble form of triggering receptor expressed on myeloid cells-1 (sTREM-1) as a diagnostic marker of serious bacterial infection in febrile infants less than three months of age. Jpn J Infect Dis 61:31–35

    PubMed  CAS  Google Scholar 

  26. Sarafidis K, Soubasi-Griva V, Piretzi K et al (2010) Diagnostic utility of elevated serum soluble triggering receptor expressed on myeloid cells (sTREM)-1 in infected neonates. Intensive Care Med 36:864–868

    Article  PubMed  CAS  Google Scholar 

  27. Wu Y, Wang F, Fan X et al (2012) Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis. Crit Care 16:R229

    Article  PubMed  PubMed Central  Google Scholar 

  28. Su L, Feng L, Zhang J et al (2011) Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study. Crit Care 15:R250

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gibot S, Béné MC, Noel R et al (2012) Combination biomarkers to diagnose sepsis in the critically Ill patient. Am J Respir Crit Care Med 186:65–71

    Article  PubMed  CAS  Google Scholar 

  30. Richeldi L, Mariani M, Losi M et al (2004) Triggering receptor expressed on myeloid cells: role in the diagnosis of lung infections. Eur Respir J 24:247–250

    Article  PubMed  CAS  Google Scholar 

  31. Huh J, Lim C-M, Koh Y et al (2008) Diagnostic utility of the soluble triggering receptor expressed on myeloid cells-1 in bronchoalveolar lavage fluid from patients with bilateral lung infiltrates. Crit Care 12:R6

    Article  PubMed  PubMed Central  Google Scholar 

  32. Determann RM, Millo JL, Gibot S et al (2005) Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia. Intensive Care Med 31:1495–1500

    Article  PubMed  Google Scholar 

  33. El Solh AA, Akinnusi ME, Peter M et al (2008) Triggering receptors expressed on myeloid cells in pulmonary aspiration syndromes. Intensive Care Med 34:1012–1019

    Article  PubMed  Google Scholar 

  34. Ramirez P, Kot P, Marti V et al (2011) Diagnostic implications of soluble triggering receptor expressed on myeloid cells-1 in patients with acute respiratory distress syndrome and abdominal diseases: a preliminary observational study. Crit Care 15:1–8

    Article  Google Scholar 

  35. Phua J, Koay ESC, Zhang D et al (2006) Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections. Eur Respir J 28:695–702

    Article  PubMed  CAS  Google Scholar 

  36. Horonenko G, Hoyt JC, Robbins RA et al (2007) Soluble triggering receptor expressed on myeloid cell-1 is increased in patients with ventilator-associated pneumonia: a preliminary report. Chest 132:58–63

    Article  PubMed  CAS  Google Scholar 

  37. Oudhuis GJ, Beuving J, Bergmans D et al (2009) Soluble triggering receptor expressed on myeloid cells-1 in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia. Intensive Care Med 35:1265–1270

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Anand NJ, Zuick S, Klesney-Tait J, Kollef MH (2009) Diagnostic implications of soluble triggering receptor expressed on myeloid cells-1 in bal fluid of patients with pulmonary infiltrates in the icu. Chest 135:641–647

    Article  PubMed  Google Scholar 

  39. Palazzo SJ, Simpson TA, Simmons JM, Schnapp LM (2012) Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as a diagnostic marker of ventilator-associated pneumonia. Respir Care 57:2052–2058

    PubMed  Google Scholar 

  40. Summah H, Tao L-L, Zhu Y-G et al (2011) Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis. BMC Infect Dis 11:280

    Article  PubMed  PubMed Central  Google Scholar 

  41. Determann RM, Weisfelt M, de Gans J et al (2006) Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis. Intensive Care Med 32:1243–1247

    Article  PubMed  CAS  Google Scholar 

  42. Bishara J, Hadari N, Shalita-Chesner M et al (2007) Soluble triggering receptor expressed on myeloid cells-1 for distinguishing bacterial from aseptic meningitis in adults. Eur J Clin Microbiol Infect Dis 26:647–650

    Article  PubMed  CAS  Google Scholar 

  43. Guanghui G, Qiaoya J, Zhenhua S (2011) Value of soluble triggering receptor expressed on myeloid cells-1 in the diagnosis of bacterial meningitis. Int J Lab Med 9:12

    Google Scholar 

  44. Determann RM, Schultz MJ, Geerlings SE (2007) Soluble triggering receptor expressed on myeloid cells-1 is not a sufficient biological marker for infection of the urinary tract. J Infect 54:e249

    Article  PubMed  Google Scholar 

  45. Determann RM, Olivier van Till JW, van Ruler O et al (2009) sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis. Cytokine 46:36–42

    Article  PubMed  CAS  Google Scholar 

  46. Lu Z, Liu Y, Dong Y et al (2011) Soluble triggering receptor expressed on myeloid cells in severe acute pancreatitis: a biological marker of infected necrosis. Intensive Care Med 38:69–75

    Article  PubMed  Google Scholar 

  47. Belibasakis GN, Öztürk V-Ö, Emingil G, Bostanci N (2014) Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in gingival crevicular fluid: association with clinical and microbiologic parameters. J Periodontol 85:204–210

    Article  PubMed  Google Scholar 

  48. Bisson C, Massin F, Lefevre PA et al (2012) Increased gingival crevicular fluid levels of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in severe periodontitis. J Clin Periodontol 39:1141–1148

    Article  PubMed  CAS  Google Scholar 

  49. Bostanci N, Öztürk VÖ, Emingil G, Belibasakis GN (2013) Elevated oral and systemic levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in periodontitis. J Dent Res 92:161–165

    Article  PubMed  CAS  Google Scholar 

  50. Jiyong J, Tiancha H, Wei C, Huahao S (2008) Diagnostic value of the soluble triggering receptor expressed on myeloid cells-1 in bacterial infection: a meta-analysis. Intensive Care Med 35:587–595

    Article  PubMed  Google Scholar 

  51. Bouadma L, Luyt CE, Tubach F et al (2010) Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 375:463–474

    Article  PubMed  CAS  Google Scholar 

  52. Giamarellos-Bourboulis EJ, Zakynthinos S, Baziaka F et al (2006) Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory mediator in sepsis. Intensive Care Med 32:237–243

    Article  PubMed  CAS  Google Scholar 

  53. Wu C-L, Lu Y-T, Kung Y-C et al (2011) Prognostic value of dynamic soluble triggering receptor expressed on myeloid cells in bronchoalveolar lavage fluid of patients with ventilator-associated pneumonia. Respirology 16:487–494

    Article  PubMed  Google Scholar 

  54. Tejera A, Santolaria F, Diez M-L et al (2007) Prognosis of community acquired pneumonia (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other mediators of the inflammatory response. Cytokine 38:117–123

    Article  PubMed  CAS  Google Scholar 

  55. Zhang J, She D, Feng D et al (2011) Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study. BMC Infect Dis 11:53

    Article  PubMed  PubMed Central  Google Scholar 

  56. Su L, Liu C, Li C et al (2012) Dynamic changes in serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and its gene polymorphisms are associated with sepsis prognosis. Inflammation 35:1833–1843

    Article  PubMed  CAS  Google Scholar 

  57. Kwofie L, Rapoport BL, Fickl H et al (2012) Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia: a pilot study. Ann Hematol 91:605–611

    Article  PubMed  CAS  Google Scholar 

  58. Müller B, Gencay MM, Gibot S et al (2007) Circulating levels of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in community-acquired pneumonia. Crit Care Med 35:990–991

    Article  PubMed  Google Scholar 

  59. Bopp C, Hofer S, Bouchon A et al (2009) Soluble TREM-1 is not suitable for distinguishing between systemic inflammatory response syndrome and sepsis survivors and nonsurvivors in the early stage of acute inflammation. Eur J Anaesthesiol 26:504–507

    Article  PubMed  CAS  Google Scholar 

  60. Gibot S (2009) Soluble triggering receptor expressed on myeloid cells 1 and the diagnosis of ventilator-associated pneumonia. Chest 136:320

    Article  PubMed  Google Scholar 

  61. Adib-Conquy M, Monchi M, Goulenok C et al (2007) Increased plasma levels of soluble triggering receptor expressed on myeloid cells 1 and procalcitonin after cardiac surgery and cardiac arrest without infection. Shock 28:406–410

    Article  PubMed  CAS  Google Scholar 

  62. Bingold TM, Pullmann B, Sartorius S et al (2011) Soluble triggering receptor on myeloid cells-1 is expressed in the course of non-infectious inflammation after traumatic lung contusion: a prospective cohort study. Crit Care 15:1–7

    Article  Google Scholar 

  63. Schenk M, Bouchon A, Birrer S et al (2005) Macrophages expressing triggering receptor expressed on myeloid cells-1 are underrepresented in the human intestine. J Immunol 174:517–524

    Article  PubMed  CAS  Google Scholar 

  64. Schenk M, Bouchon A, Seibold F, Mueller C (2007) TREM-1–expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. J Clin Invest 117:3097–3106

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  65. Park JJ, Cheon JH, Kim BY et al (2009) Correlation of serum-soluble triggering receptor expressed on myeloid cells-1 with clinical disease activity in inflammatory bowel disease. Dig Dis Sci 54:1525–1531

    Article  PubMed  CAS  Google Scholar 

  66. Jung YS, Park JJ, Kim SW et al (2012) Correlation between soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) expression and endoscopic activity in inflammatory bowel diseases. Dig Liver Dis 44:897–903

    Article  PubMed  CAS  Google Scholar 

  67. Tzivras M, Koussoulas V, Giamarellos-Bourboulis EJ et al (2006) Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease. World J Gastroenterol 12:3416

    PubMed  CAS  PubMed Central  Google Scholar 

  68. Billioud V, Gibot S, Massin F et al (2012) Plasma soluble triggering receptor expressed on myeloid cells-1 in Crohn’s disease. Dig Liver Dis 44:466–470

    Article  PubMed  CAS  Google Scholar 

  69. Saurer L, Rihs S, Birrer M et al (2012) Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1 in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and endoscopic disease activity. J Crohns Colitis 6:913–923

    Article  PubMed  Google Scholar 

  70. Koussoulas V, Tzivras M, Giamarellos-Bourboulis EJ et al (2007) Can soluble triggering receptor expressed on myeloid cells (sTREM-1) be considered an anti-inflammatory mediator in the pathogenesis of peptic ulcer disease? Dig Dis Sci 52:2166–2169

    Article  PubMed  CAS  Google Scholar 

  71. Koussoulas V, Giamarellos-Bourboulis EJ, Barbatzas C, Pimentel M (2011) Serum sTREM-1 as a surrogate marker of treatment outcome in patients with peptic ulcer disease. Dig Dis Sci 56:3590–3595

    Article  PubMed  CAS  Google Scholar 

  72. Radsak MP, Taube C, Haselmayer P et al (2007) Soluble triggering receptor expressed on myeloid cells 1 is released in patients with stable chronic obstructive pulmonary disease. Clin Dev Immunol 2007:52040

    Article  PubMed  PubMed Central  Google Scholar 

  73. Rohde G, Radsak MP, Borg I et al (2012) Levels of soluble triggering receptor expressed on myeloid cells 1 in infectious exacerbations of chronic obstructive pulmonary disease. Respiration 83:133–139

    Article  PubMed  Google Scholar 

  74. Collins CE, La DT, Yang H-T et al (2009) Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis. Ann Rheum Dis 68:1768–1774

    Article  PubMed  CAS  Google Scholar 

  75. Daikeler T, Regenass S, Tyndall A et al (2008) Increased serum levels of soluble triggering receptor expressed on myeloid cells-1 in antineutrophil cytoplasmic antibody-associated vasculitis. Ann Rheum Dis 67:723–724

    Article  PubMed  CAS  Google Scholar 

  76. Molad Y, Pokroy-Shapira E, Kaptzan T et al (2013) Serum soluble triggering receptor on myeloid cells-1 (sTREM-1) is elevated in systemic lupus erythematosus but does not distinguish between lupus alone and concurrent infection. Inflammation 1–6:1519–1524

    Article  Google Scholar 

  77. Gibot S, Alauzet C, Massin F et al (2006) Modulation of the triggering receptor expressed on myeloid cells–1 pathway during pneumonia in rats. J Infect Dis 194:975–983

    Article  PubMed  CAS  Google Scholar 

  78. Wiersinga WJ, van’t Veer C, Wieland CW et al (2007) Expression profile and function of triggering receptor expressed on myeloid cells-1 during melioidosis. J Infect Dis 196:1707–1716

    Article  PubMed  CAS  Google Scholar 

  79. Kamei K, Yasuda T, Ueda T et al (2010) Role of triggering receptor expressed on myeloid cells-1 in experimental severe acute pancreatitis. J Hepatobiliary Pancreat Sci 17:305–312

    Article  PubMed  Google Scholar 

  80. Gibot S, Massin F, Alauzet C et al (2009) Effects of the TREM 1 pathway modulation during hemorrhagic shock in rats. Shock 32:633–637

    Article  PubMed  Google Scholar 

  81. Gibot S, Massin F, Alauzet C et al (2008) Effects of the TREM-1 pathway modulation during mesenteric ischemia-reperfusion in rats. Crit Care Med 36:504–510

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Intensive Care, Hôpital Central, 29 avenue du Maréchal de Lattre de Tassigny, 54035, Nancy Cedex, France

    Jérémie Lemarié, Damien Barraud & Sébastien Gibot

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  1. Jérémie Lemarié
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  2. Damien Barraud
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  3. Sébastien Gibot
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Correspondence to Sébastien Gibot .

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  1. University Vita-Salute San Raffaele, Milan, Italy

    Nicasio Mancini

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Lemarié, J., Barraud, D., Gibot, S. (2015). Host Response Biomarkers in Sepsis: Overview on sTREM-1 Detection. In: Mancini, N. (eds) Sepsis. Methods in Molecular Biology, vol 1237. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1776-1_17

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  • DOI: https://doi.org/10.1007/978-1-4939-1776-1_17

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