Clinical value of peripheral serum cf-DNA/NETs level in diagnosis and severity assessment of sepsis patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

MENG Qiang ,  QU Feng , DONG Wei , ZHANG Hao

Intensive Care Unit, The First People’s Hospital of Jining, Jining, Shandong 272011, P. R. China;

Corresponding?author：

QU Feng, Email: 87565594@qq.com

Keywords：

Neutrophil extracellular traps; Sepsis; Procalcitonin; Systemic inflammatory response syndrome

DOI：

10.7507/1671-6205.201706035

Video：

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Objective To investigate the clinical value of peripheral serum cell-free DNA/neutrophil extracellular traps (cf-DNA/NETs) level in diagnosis and severity assessment of sepsis patients. Methods Forty patients with sepsis and 40 patients with non-infectious systemic inflammatory response syndrome (nf-SIRS) were enrolled in this study. The cf-DNA/NETs level in serum of all subjects were measured. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of the cf-DNA/NETs, white blood cell count (WBC), procalcitonin (PCT) and interleukin-6 (IL-6). The sepsis patients were stratified into a survival group and a death group according to the prognosis. Sequential organ failure (SOFA) score were recorded in the sepsis patients, and the correlations between SOFA and cf-DNA/NETs, PCT, WBC, IL-6 were analyzed. Results Compared with the nf-SIRS group, cf-DNA/NETs and PCT levels were significantly higher in the sepsis group (both P<0.05). WBC and IL-6 showed no significant differences between the two groups (bothP>0.05). The area under the ROC curve (AUC) of cf-DNA/NETs was 0.884 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803). The cf-DNA/NETs showed better sensitivity (81.2% and 79.2%) and specificity (81.0% and 82.4%) than PCT. cf-DNA/NETs and PCT were significantly higher in the death group than those in the survival group. Bivariate collection analysis revealed positive correlations between SOFA score and the two biomarkers of cf-DNA/NETs and PCT (r₁=0.573, r₂=0.518; both P<0.01). Conclusions cf-DNA/NETs and PCT have certain value in early diagnosis of sepsis, and cf-DNA/NETs shows better diagnostic value in distinguishing sepsis from nf-SIRS than PCT. cf-DNA/NETs can be used as a routine monitoring index to help assess disease severity in sepsis.

Citation： MENG Qiang, QU Feng, DONG Wei, ZHANG Hao. Clinical value of peripheral serum cf-DNA/NETs level in diagnosis and severity assessment of sepsis patients. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(3): 255-258. doi: 10.7507/1671-6205.201706035 Copy

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4.	Remijsen Q, Kuijpers TW, Wirawan E, et al. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ, 2011, 18(4): 581-588.
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8.	張春容, 陶武. 外周血 cf-DNA/NETs 水平在膿毒癥患者中的臨床價值研究. 重慶醫學, 2015, 44(20): 2740-2742.
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11.	Rusconi AM, Bossi I, Lampard JG, et al. Early goal-directed therapy vs usual care in the treatment of severe sepsis and septic shock: a systematic review and meta-analysis. Intern Emerg Med, 2015, 10(6): 731-743.
12.	Liu B, Ding X, Yang J. Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock. Curr Med Res Opin, 2016, 32(11): 1773-1782.
13.	單亮, 修建榮, 李秀, 等. 膿毒癥早期診斷生物標志物的再評價. 中華危重病急救醫學, 2015(6): 538-540.
14.	念學武, 孫二琳, 韓瑞發. 中性粒細胞免疫調節作用的研究進展. 國際免疫學雜志, 2014, 37(5): 394-397.
15.	Martinod K, Witsch T, Farley K, et al. Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis. J Thromb Haemost, 2016, 14(3): 551-558.
16.	Camicia G, Pozner R, De Larranaga G. Neutrophil extracellular traps in sepsis. Shock, 2014, 42(4): 286-294.
17.	Ammollo CT, Semeraro F, Xu J, et al. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost, 2011, 9(9): 1795-1803.
18.	Long W, Deng X, Zhang Y, et al. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Respirology, 2011, 16(5): 819-824.
19.	Tang BM, Eslick GD, Craig JC, et al. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis, 2007, 7(3): 210-217.
20.	Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med, 2007, 13(4): 463-469.
21.	Dandona P, Nix D, Wilson MF, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab, 1994, 79(6): 1605-1608.
22.	Calandra T, Gerain J, Heumann D, et al. High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss-Dutch J5 Immunoglobulin Study Group. Am J Med, 1991, 91(1): 23-29.

1. Du B, An Y, Kang Y, et al. Characteristics of critically ill patients in ICUs in mainland China. Crit Care Med, 2013, 41(1): 84-92.
2. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med, 2013, 39(2): 165-228.
3. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science, 2004, 303(5663): 1532-1535.
4. Remijsen Q, Kuijpers TW, Wirawan E, et al. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ, 2011, 18(4): 581-588.
5. Logters T, Paunel-Gorgulu A, Zilkens C, et al. Diagnostic accuracy of neutrophil-derived circulating free DNA (cf-DNA/NETs) for septic arthritis. J Orthop Res, 2009, 27(11): 1401-1407.
6. Margraf S, Logters T, Reipen J, et al. Neutrophil-derived circulating free DNA (cf-DNA/NETs): a potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis. Shock, 2008, 30(4): 352-358.
7. Hirose T, Hamaguchi S, Matsumoto N, et al. Presence of neutrophil extracellular traps and citrullinated histone H3 in the bloodstream of critically ill patients. PLoS One, 2014, 9(11): e111755.
8. 張春容, 陶武. 外周血 cf-DNA/NETs 水平在膿毒癥患者中的臨床價值研究. 重慶醫學, 2015, 44(20): 2740-2742.
9. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med, 2003, 31(4): 1250-1256.
10. Kambas K, Mitroulis I, Apostolidou E, et al. Autophagy mediates the delivery of thrombogenic tissue factor to neutrophil extracellular traps in human sepsis. PLoS One, 2012, 7(9): e45427.
11. Rusconi AM, Bossi I, Lampard JG, et al. Early goal-directed therapy vs usual care in the treatment of severe sepsis and septic shock: a systematic review and meta-analysis. Intern Emerg Med, 2015, 10(6): 731-743.
12. Liu B, Ding X, Yang J. Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock. Curr Med Res Opin, 2016, 32(11): 1773-1782.
13. 單亮, 修建榮, 李秀, 等. 膿毒癥早期診斷生物標志物的再評價. 中華危重病急救醫學, 2015(6): 538-540.
14. 念學武, 孫二琳, 韓瑞發. 中性粒細胞免疫調節作用的研究進展. 國際免疫學雜志, 2014, 37(5): 394-397.
15. Martinod K, Witsch T, Farley K, et al. Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis. J Thromb Haemost, 2016, 14(3): 551-558.
16. Camicia G, Pozner R, De Larranaga G. Neutrophil extracellular traps in sepsis. Shock, 2014, 42(4): 286-294.
17. Ammollo CT, Semeraro F, Xu J, et al. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost, 2011, 9(9): 1795-1803.
18. Long W, Deng X, Zhang Y, et al. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Respirology, 2011, 16(5): 819-824.
19. Tang BM, Eslick GD, Craig JC, et al. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis, 2007, 7(3): 210-217.
20. Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med, 2007, 13(4): 463-469.
21. Dandona P, Nix D, Wilson MF, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab, 1994, 79(6): 1605-1608.
22. Calandra T, Gerain J, Heumann D, et al. High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. The Swiss-Dutch J5 Immunoglobulin Study Group. Am J Med, 1991, 91(1): 23-29.

Chinese Journal of Respiratory and Critical Care Medicine

Clinical value of peripheral serum cf-DNA/NETs level in diagnosis and severity assessment of sepsis patients

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