Sepsis Biomarkers

biyomedikalozel5-1-24kapak

Ali Necati GÖKMENa , Ejder Kamil ÖZTÜRKb
aDokuz Eylül University Faculty of Medicine, Department of Anesthesiology and Reanimation, Subdivision of Critical Care Medicine, İzmir, Türkiye
bDokuz Eylül University Faculty of Medicine, Department of Internal Medicine, Subdivision of Critical Care Medicine, İzmir, Türkiye

Gökmen AN, Öztürk EK. Sepsis biomarkers. In: Koçdor H, Pabuççuoğlu A, Zihnioğlu F, eds. Inflammation and in vitro Diagnostics. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.38-43.

Article Language: EN

ABSTRACT
Sepsis is a clinical syndrome that includes physiological, biological, and biochemical abnormalities due to the dysregulation of the host’s response to infection. Sepsis and the resulting inflammatory response can lead to multiple organ dysfunction syndromes (MODS) and death. Early diagnosis and prompt antibiotic prescription are essential in treating bacterial sepsis. Providing a timely distinction between infectious and non-infectious patients is often challenging. Some biomarkers have been used to help diagnose sepsis and determine disease severity and prognosis. Unfortunately, a biomarker with sufficient sensitivity and specificity to diagnose or exclude sepsis has not yet been identified. About 200 different biomarkers related to sepsis have been studied. Several biomarkers have been identified for sepsis. Liquid Phase Pattern Recognition Molecules (PRMs), cytokines and chemokines, complement systems, Damage-Associated Molecular Pattern (DAMPs), cell membrane receptors, micro RNAs (miRNA), noncoding RNAs (ncRNA), cell proteins, metabolites, and soluble receptors are some of them. Classical biomarkers such as C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Procalcitonin (PCT) are the best known. However, the need to identify good combinations remains.

Keywords: Sepsis; biomarkers

Referanslar

  1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-10. [Crossref]  [PubMed]  [PMC]
  2. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 2014;42(3):625. [Crossref]  [PubMed]  [PMC]
  3. Investigators P. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-93. [Crossref]  [PubMed]  [PMC]
  4. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-96. [Crossref]  [PubMed]
  5. Van Engelen TSR, Wiersinga WJ, Scicluna BP, van der Poll T. Biomarkers in sepsis. Crit Care Clin. 2018;34(1):139-52. [Crossref]  [PubMed]
  6. Prucha M. Bellingan G. Zazula R. Sepsis biomarkers Clin Chim Acta. 2015;440:97-103. [Crossref]  [PubMed]
  7. Pierrakos C, Vincent J-L. Sepsis biomarkers: a review. Crit care. 2010;14(1):1-18. [Crossref]  [PubMed]  [PMC]
  8. Erreni M, Manfredi AA, Garlanda C, Mantovani A, Rovere‐Querini P. The long pentraxin PTX 3: A prototypical sensor of tissue injury and a regulator of homeostasis. Immunol Rev. 2017;280(1):112-25. [Crossref]  [PubMed]
  9. Reinhart K, Menges T, Gardlund B, Zwaveling JH, Smithes M, Vincent JL, et al. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study. Crit Care Med. 2001;29(4):765-9. [Crossref]  [PubMed]
  10. Shehabi Y, Seppelt I. Pro/Con debate: is procalcitonin useful for guiding antibiotic decision making in critically ill patients? Crit Care. 2008;12(3):1-5. [Crossref]  [PubMed]  [PMC]
  11. Pierrakos C, Velissaris D, Bisdorff M, Marshall JC, Vincent J-L. Biomarkers of sepsis: time for a reappraisal. Crit Care. 2020;24(1):1-15. [Crossref]  [PubMed]  [PMC]
  12. Lobo SMA, Lobo FRM, Bota DP, Lopes-Ferreira F, Soliman HM, Meélot C, et al. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest. 2003;123(6):2043-9. [Crossref]  [PubMed]
  13. Caironi P, Masson S, Mauri T, Bottazzi B, Leone R, Magnoli M, et al. Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial. Eur J Clin Invest. 2017;47(1):73-83. [Crossref]  [PubMed]  [PMC]
  14. Song J, Moon S, Park DW, Cho HJ, Kim JY, Park J, et al. Biomarker combination and SOFA score for the prediction of mortality in sepsis and septic shock: A prospective observational study according to the Sepsis-3 definitions. Medicine (Baltimore). 2020;99(22):e20495. [Crossref]  [PubMed]
  15. Ljungström L, Pernestig AK, Jacobsson G, Andersson R, Usener B, Tilevik D. Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One. 2017;12(7):e0181704. [Crossref]  [PubMed]  [PMC]
  16. Younger JG, Bracho DO, Chung‐Esaki HM, Lee M, Rana GK, Sen A, et al. Complement activation in emergency department patients with severe sepsis. Acad Emerg Med. 2010;17(4):353-9. [Crossref]  [PubMed]  [PMC]
  17. Matsumoto H, Ogura H, Shimizu K, Ikeda M, Hirose T, Matsuura H, et al. The clinical importance of a cytokine network in the acute phase of sepsis. Sci Rep. 2018;8(1):1-11. [Crossref]  [PubMed]  [PMC]
  18. Sibbing D, Koch W, Massberg S, Byrne RA, Mehilli J, Schulz S, et al. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J. 2011;32(13):1605-13. [Crossref]  [PubMed]
  19. Hirano T. Interleukin 6 (IL‐6) and its receptor: their role in plasma cell neoplasias. Int J Cell Cloning. 1991;9(3):166-84. [Crossref]  [PubMed]
  20. Bloos F, Reinhart K. Rapid diagnosis of sepsis. Virulence. 2014;5(1):154-60. [Crossref]  [PubMed]  [PMC]
  21. Oda S, Hirasawa H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis. Cytokine. 2005;29(4):169-75. [Crossref]  [PubMed]
  22. Iwase S, Nakada T, Hattori N, Takahashi W, Takahashi N, Aizimu T, et al. Interleukin-6 as a diagnostic marker for infection in critically ill patients: a systematic review and meta-analysis. Am J Emerg Med. 2019;37(2):260-5. [Crossref]  [PubMed]
  23. Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167(15):1655-63. [Crossref]  [PubMed]  [PMC]
  24. Larsson A, Tydén J, Johansson J, Lipcsey M, Bergquist M, Kultima K, et al. Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients. Scand J Clin Lab Invest. 2020;80(2):156-61. [Crossref]  [PubMed]
  25. Barichello T, Generoso JS, Collodel A, Petronilho F, Dal-Pizzol F. The blood-brain barrier dysfunction in sepsis. Tissue Barriers. 2021;9(1):1840912. [Crossref]  [PubMed]  [PMC]
  26. Zhao GJ, Li D, Zhao Q, Lian J, Hu TT, Hong G, et al. Prognostic value of plasma tight-junction proteins for sepsis in emergency department: an observational study. Shock. 2016;45(3):326-32. [Crossref]  [PubMed]
  27. Skibsted S, Jones AE, Puskarich MA, Arnold R, Sherwin R, Trzeciak S, et al. Biomarkers of endothelial cell activation in early sepsis. Shock. 2013;39(5):427. [Crossref]  [PubMed]  [PMC]
  28. Erikson K, Ala‐Kokko TI, Koskenkari J, Liisanantti JH, Kamakura R, Herzig KH, et al. Elevated serum S‐100β in patients with septic shock is associated with delirium. Acta Anaesthesiol Scand. 2019;63(1):69-73. [Crossref]  [PubMed]
  29. Ikeda M, Matsumoto H, Ogura H, Hirose T, Shimizu K, Yamamoto K, et al. Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis. J Crit Care. 2018;43:48-53. [Crossref]  [PubMed]
  30. Mahmoodpoor A, Movassaghpour A, Talebi M, Shadvar K, Soleimanpour H. Value of flow cytometry (HLA-DR, CD14, CD25, CD13, CD64) in prediction of prognosis in critically ill septic patients admitted to ICU: A pilot study. J Clin Anesth. 2019;61:109646. [Crossref]  [PubMed]
  31. Yin W, Li J, Zheng X, An L, Shao H, Li C. Effect of neutrophil CD64 for diagnosing sepsis in emergency department. World J Emerg Med. 2020;11(2):79. [Crossref]  [PubMed]  [PMC]
  32. Kondo Y, Umemura Y, Hayashida K, Hara Y, Aihara M, Yamakawa K. Diagnostic value of procalcitonin and presepsin for sepsis in critically ill adult patients: a systematic review and meta-analysis. J Intensive Care. 2019;7(1):1-13. [Crossref]  [PubMed]  [PMC]
  33. Şen S, Kamit F, İşgüder R, Bal ZŞ, Devrim İ, Bayram SN, et al. Surface TREM-1 as a prognostic biomarker in pediatric sepsis. Indian J Pediatr. 2021;88(2):134-40. [Crossref]  [PubMed]
  34. Assimakopoulos SF, Triantos C, Thomopoulos K, Fligou F, Maroulis I, Marangos M, et al. Gut-origin sepsis in the critically ill patient: pathophysiology and treatment. Infection. 2018;46(6):751-60. [Crossref]  [PubMed]
  35. Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, et al. Increased plasma zonulin in patients with sepsis. Biochem Medica. 2013;23(1):107-11. [Crossref]  [PubMed]  [PMC]
  36. Zhang X, Liu D, Wang Y, Yan J, Yang X. Clinical significance on serum intestinal fatty acid binding protein and D-lactic acid levels in early intestinal injury of patients with sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019;31(5):545-50.
  37. Reinhart K, Karzai W, Meisner M. Procalcitonin as a marker of the systemic inflammatory response to infection. Intensive Care Med. 2000;26(9):1193. [Crossref]  [PubMed]  [PMC]
  38. Klouche K, Cristol JP, Devin J, Gilles V, Kuster N, Larcher R, et al. Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients. Ann Intensive Care. 2016;6(1):1-11. [Crossref]  [PubMed]  [PMC]
  39. Elke G, Bloos F, Wilson DC, Brunkhorst FM, Briegel J, Reinhart K, et al. The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis-a secondary analysis of a large randomised controlled trial. Crit Care. 2018;22(1):1-12. [Crossref]  [PubMed]  [PMC]
  40. Honore PM, Redant S, De Bels D. Reliability of biomarkers of sepsis during extracorporeal therapies: the clinician needs to know what is eliminated and what is not. Vol. 24, Critical Care. BioMed Central; 2020. p.1-4. [Crossref]  [PubMed]  [PMC]
  41. Custodero C, Wu Q, Ghita GL, Anton SD, Brakenridge SC, Brumback BA, et al. Prognostic value of NT-proBNP levels in the acute phase of sepsis on lower long-term physical function and muscle strength in sepsis survivors. Crit Care. 2019;23(1):1-11. [Crossref]  [PubMed]  [PMC]
  42. Varpula M, Pulkki K, Karlsson S, Ruokonen E, Pettilä V, Group FS. Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock. Crit Care Med. 2007;35(5):1277-83. [Crossref]  [PubMed]
  43. Eggimann P, Que YA, Rebeaud F. Measurement of pancreatic stone protein in the identification and management of sepsis. Biomark Med. 2019;13(02):135-45. [Crossref]  [PubMed]
  44. Fidalgo P, Nora D, Coelho L, Povoa P. Pancreatic Stone Protein: Review of a New Biomarker in Sepsis. J Clin Med. 2022;11(4):1085. [Crossref]  [PubMed]  [PMC]
  45. Liu W, Geng F, Yu L. Long non‐coding RNA MALAT1/microRNA 125a axis presents excellent value in discriminating sepsis patients and exhibits positive association with general disease severity, organ injury, inflammation level, and mortality in sepsis patients. J Clin Lab Anal. 2020;34(6):e23222. [Crossref]  [PubMed]  [PMC]
  46. Na L, Ding H, Xing E, Gao J, Liu B, Wang H, et al. Lnc‐MEG3 acts as a potential biomarker for predicting increased disease risk, systemic inflammation, disease severity, and poor prognosis of sepsis via interacting with miR‐21. J Clin Lab Anal. 2020;34(4):e23123. [Crossref]  [PubMed]  [PMC]
  47. Zhao D, Li S, Cui J, Wang L, Ma X, Li Y. Plasma miR‐125a and miR‐125b in sepsis: correlation with disease risk, inflammation, severity, and prognosis. J Clin Lab Anal. 2020;34(2):e23036. [Crossref]  [PubMed]  [PMC]
  48. Cao C, Gu J, Zhang J. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases. Front Med. 2017;11(2):169-77. [Crossref]  [PubMed]
  49. Anderson BJ, Calfee CS, Liu KD, Reilly JP, Kangelaris KN, Shashaty MGS, et al. Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study. Crit Care. 2019;23(1):1-9. [Crossref]  [PubMed]  [PMC]
  50. Teggert A, Datta H, Ali Z. Biomarkers for point-of-care diagnosis of sepsis. Micromachines. 2020;11(3):286. [Crossref]  [PubMed]  [PMC]
  51. Sharma A, Ray S, Mamidipalli R, Kakar A, Chugh P, Jain R, et al. A comparative study of the diagnostic and prognostic utility of soluble urokinase-type plasminogen activator receptor and procalcitonin in patients with sepsis and systemic inflammation response syndrome. Indian J Crit Care Med Peer-reviewed, Off Publ Indian Soc Crit Care Med. 2020;24(4):245. [Crossref]  [PubMed]  [PMC]
  52. Liu M, Zhang X, Chen H, Wang G, Zhang J, Dong P, et al. Serum sPD‐L1, upregulated in sepsis, may reflect disease severity and clinical outcomes in septic patients. Scand J Immunol. 2017;85(1):66-72. [Crossref]  [PubMed]
  53. Bonaventura A, Carbone F, Vecchié A, Meessen J, Ferraris S, Beck E, et al. The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial. Eur J Clin Invest. 2020;50(10):e13333. [Crossref]  [PubMed]
  54. Osuchowski MF, Ayala A, Bahrami S, Bauer M, Boros M, Cavaillon JM, et al. Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis. Intensive care Med Exp. 2018;6(1):1-6. [Crossref]  [PubMed]  [PMC]
  55. Osuchowski MF, Connett J, Welch K, Granger J, Remick DG. Stratification is the key: inflammatory biomarkers accurately direct immunomodulatory therapy in experimental sepsis. Crit Care Med. 2009;37(5):1567. [Crossref]  [PubMed]  [PMC]
  56. Turnbull IR, Javadi P, Buchman TG, Hotchkiss RS, Karl IE, Coopersmith CM. Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels. Shock. 2004;21(2):121-5. [Crossref]  [PubMed]