Value of peripheral blood soluble triggering receptor expressed on myeloid cells-1 and myeloid cell membrane-bound triggering receptor expressed on myeloid cells-1 in disease stratification of sepsis_West China Medical Journal

Authors：

WANG Shuang ^1,2,3 , MENG Qiang ^1,2,3 , HUANG Qian ^1,2,3 ,  FU Yang ^1,2,3

1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Sichuan Provincial Clinical Research Center for Laboratory Medicine, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

FU Yang, Email: fuyang827@wchscu.cn

Keywords：

Sepsis; triggering receptor expressed on myeloid cells -1; diagnostic performance

DOI：

10.7507/1002-0179.202607100

Video：

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Objective To analyze the expression changes of peripheral blood triggering receptor expressed on myeloid cells-1 (TREM-1) during the progression of sepsis, and to explore the utility of soluble TREM-1 (sTREM-1) and membrane-bound TREM-1 on myeloid cells in disease stratification of sepsis. Methods Sepsis patients, septic shock patients, and healthy controls were enrolled from West China Hospital of Sichuan University between June to December 2022. Membrane-bound TREM-1 expression on peripheral blood myeloid cells was detected by flow cytometry, and serum sTREM-1 levels were measured by enzyme-linked immunosorbent assay. The diagnostic performance of TREM-1-related parameters for discriminating sepsis from septic shock was evaluated by receiver operating characteristic curves. Results A total of 72 samples were collected. Among them, there were 10 healthy controls, 28 sepsis patients, and 34 septic shock patients. Peripheral blood sTREM-1, TREM-1⁺ granulocytes, and TREM-1⁺ monocytes showed significant differences among the sepsis, septic shock, and healthy control groups (P<0.05). For discriminating sepsis from septic shock, sTREM-1 yielded a sensitivity of 62.1% and a specificity of 88.9%; TREM-1⁺ granulocytes had a sensitivity of 65.5% and a specificity of 77.8%; and TREM-1⁺ monocytes had a sensitivity of 65.5% and a specificity of 66.7%. The combined model of the three indicators generated a predicted probability with an area under the curve of 0.881 [95% confidence interval (0.785, 0.978)], a sensitivity of 93.1%, and a specificity of 66.7%. Conclusions The expression of membrane-bound TREM-1 on peripheral blood granulocytes and monocytes, as well as serum sTREM-1, differs during sepsis progression and demonstrates auxiliary value in identifying disease stratification of sepsis. These parameters may serve as laboratory indicators for assessing the severity of sepsis.

Citation： WANG Shuang, MENG Qiang, HUANG Qian, FU Yang. Value of peripheral blood soluble triggering receptor expressed on myeloid cells-1 and myeloid cell membrane-bound triggering receptor expressed on myeloid cells-1 in disease stratification of sepsis. West China Medical Journal, 2026, 41(8): 1259-1264. doi: 10.7507/1002-0179.202607100 Copy

1.	Xiao F, Wang D, Kong L, et al. Intermedin protects against sepsis by concurrently re-establishing the endothelial barrier and alleviating inflammatory responses[J]. Nat Commun, 2018, 9(1): 2644.
2.	Booty LM, Bryant CE. Gasdermin D and beyond - gasdermin-mediated pyroptosis in bacterial infections[J]. J Mol Biol, 2022, 434(4): 167409.
3.	Zi Y, Yi-An Y, Bing J, et al. Sirt6-induced autophagy restricted TREM-1-mediated pyroptosis in ox-LDL-treated endothelial cells: relevance to prognostication of patients with acute myocardial infarction[J]. Cell Death Discov, 2019, 12(5): 88-102.
4.	de Oliveira Matos A, Dos Santos Dantas PH, Figueira Marques Silva-Sales M, et al. The role of the triggering receptor expressed on myeloid cells-1 (TREM-1) in non-bacterial infections[J]. Crit Rev Microbiol, 2020, 46(3): 237-252.
5.	張慧芳, 張雪, 沙玉霞, 等. 血清及支氣管肺泡灌洗液中 sTREM-1 水平、APACHEⅡ評分及 SOFA 評分對重癥肺炎患兒病情及預后評價[J]. 中國當代兒科雜志, 2020, 22(6): 626-631.
6.	Frederic R, Matthias K, Nora SL, et al. Characterization of TREM-1 signaling in human neutrophils by kinome array and RNA-seq[J]. Blood, 2023, 142(Suppl 1): 3913.
7.	Jolly L, Carrasco K, Derive M, et al. Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock[J]. Cardiovasc Res, 2018, 114(6): 907-918.
8.	Theobald V, Schmitt FCF, Middel CS, et al. Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies[J]. Crit Care, 2024, 28(1): 17.
9.	Boufenzer A, Carrasco K, Jolly L, et al. Potentiation of NETs release is a novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis[J]. Cell Mol Immunol, 2021, 18(2): 452-460.
10.	Poukoulidou T, Spyridaki A, Mihailidou I, et al. TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen[J]. BMC Infect Dis, 2011, 4(11): 309.
11.	Marioli A, Koupetori M, Raftogiannis M, et al. Early changes of the kinetics of monocyte Trem-1 reflect final outcome in human sepsis[J]. BMC Immunol, 2014(15): 585.
12.	Carrasco K, Boufenzer A, Jolly L, et al. TREM-1 multimerization is essential for its activation on monocytes and neutrophils[J]. Cell Mol Immunol, 2019, 16(5): 460-472.
13.	Jiang S, Liu L, Zhu X. Correlation of serum H-FABP, sTREM-1, and HMGB1 levels with severity and prognosis of sepsis[J]. Am J Transl Res, 2024, 16(10): 5846-5855.
14.	Zheng F. Pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure and diagnostic value of sTREM-1, sCD163, and sTWEAK[J/OL]. Pak J Med Sci, 2022, 38(3Part-I): 536-541. DOI: 10.12669/pjms.38.3.4758.
15.	Gibot S, Cravoisy A. Soluble form of the triggering receptor expressed on myeloid cells-1 as a marker of microbial infection[J]. Clin Med Res, 2004, 2(3): 181-187.
16.	Gibot S. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia and severe sepsis[J]. Semin Respir Crit Care Med, 2006, 27(1): 29-33.
17.	Sathe NA, Bhatraju PK, Mikacenic C, et al. Relationships between age, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and mortality among critically ill adults: a cohort study[J]. Shock, 2022, 57(2): 205-211.
18.	Bautista-Carbajal P, Chávez-Pérez JP, García-León ML, et al. sTREM-1 as a biomarker for sepsis diagnosis and prognosis following abdominal surgery[J]. Lab Med, 2026, 57(1): lmaf074.
19.	Cabral JVB, da Silveira MMBM, Vasconcelos WTF, et al. Sepsis prediction: biomarkers combined in a bayesian approach[J]. Int J Mol Sci, 2025, 26(15): 7379.
20.	Khuchua E, Didbaridze T, Ormotsadze G, et al. Evaluating the diagnostic and prognostic value of interleukin-6 (IL-6) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in systemic inflammatory response syndrome (SIRS) and sepsis in adults[J/OL]. Cureus, 2024, 16(11): e73310. DOI: 10.7759/cureus.73310.
21.	Gibot S, Lafon T, Jacquin L, et al. Soluble TREM-1 plasma concentration predicts poor outcome in COVID-19 patients[J]. Intensive Care Med Exp, 2023, 11(1): 51.
22.	Matos AO, Dantas PHDS, Silva-Sales M, et al. TREM-1 isoforms in bacterial infections: to immune modulation and beyond[J]. Crit Rev Microbiol, 2021, 47(3): 290-306.
23.	Weiss G, Lai C, Fife ME, et al. Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors[J]. Mucosal Immunol, 2017, 10(4): 1021-1030.
24.	Eman R, Mona M. Saber N, et al. TREM-1 receptor: a key player in inflammatory diseases[J]. Curr Mol Pharmacol, 2026, 19(1): 41-47.

1. Xiao F, Wang D, Kong L, et al. Intermedin protects against sepsis by concurrently re-establishing the endothelial barrier and alleviating inflammatory responses[J]. Nat Commun, 2018, 9(1): 2644.
2. Booty LM, Bryant CE. Gasdermin D and beyond - gasdermin-mediated pyroptosis in bacterial infections[J]. J Mol Biol, 2022, 434(4): 167409.
3. Zi Y, Yi-An Y, Bing J, et al. Sirt6-induced autophagy restricted TREM-1-mediated pyroptosis in ox-LDL-treated endothelial cells: relevance to prognostication of patients with acute myocardial infarction[J]. Cell Death Discov, 2019, 12(5): 88-102.
4. de Oliveira Matos A, Dos Santos Dantas PH, Figueira Marques Silva-Sales M, et al. The role of the triggering receptor expressed on myeloid cells-1 (TREM-1) in non-bacterial infections[J]. Crit Rev Microbiol, 2020, 46(3): 237-252.
5. 張慧芳, 張雪, 沙玉霞, 等. 血清及支氣管肺泡灌洗液中 sTREM-1 水平、APACHEⅡ評分及 SOFA 評分對重癥肺炎患兒病情及預后評價[J]. 中國當代兒科雜志, 2020, 22(6): 626-631.
6. Frederic R, Matthias K, Nora SL, et al. Characterization of TREM-1 signaling in human neutrophils by kinome array and RNA-seq[J]. Blood, 2023, 142(Suppl 1): 3913.
7. Jolly L, Carrasco K, Derive M, et al. Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock[J]. Cardiovasc Res, 2018, 114(6): 907-918.
8. Theobald V, Schmitt FCF, Middel CS, et al. Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies[J]. Crit Care, 2024, 28(1): 17.
9. Boufenzer A, Carrasco K, Jolly L, et al. Potentiation of NETs release is a novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis[J]. Cell Mol Immunol, 2021, 18(2): 452-460.
10. Poukoulidou T, Spyridaki A, Mihailidou I, et al. TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen[J]. BMC Infect Dis, 2011, 4(11): 309.
11. Marioli A, Koupetori M, Raftogiannis M, et al. Early changes of the kinetics of monocyte Trem-1 reflect final outcome in human sepsis[J]. BMC Immunol, 2014(15): 585.
12. Carrasco K, Boufenzer A, Jolly L, et al. TREM-1 multimerization is essential for its activation on monocytes and neutrophils[J]. Cell Mol Immunol, 2019, 16(5): 460-472.
13. Jiang S, Liu L, Zhu X. Correlation of serum H-FABP, sTREM-1, and HMGB1 levels with severity and prognosis of sepsis[J]. Am J Transl Res, 2024, 16(10): 5846-5855.
14. Zheng F. Pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure and diagnostic value of sTREM-1, sCD163, and sTWEAK[J/OL]. Pak J Med Sci, 2022, 38(3Part-I): 536-541. DOI: 10.12669/pjms.38.3.4758.
15. Gibot S, Cravoisy A. Soluble form of the triggering receptor expressed on myeloid cells-1 as a marker of microbial infection[J]. Clin Med Res, 2004, 2(3): 181-187.
16. Gibot S. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia and severe sepsis[J]. Semin Respir Crit Care Med, 2006, 27(1): 29-33.
17. Sathe NA, Bhatraju PK, Mikacenic C, et al. Relationships between age, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and mortality among critically ill adults: a cohort study[J]. Shock, 2022, 57(2): 205-211.
18. Bautista-Carbajal P, Chávez-Pérez JP, García-León ML, et al. sTREM-1 as a biomarker for sepsis diagnosis and prognosis following abdominal surgery[J]. Lab Med, 2026, 57(1): lmaf074.
19. Cabral JVB, da Silveira MMBM, Vasconcelos WTF, et al. Sepsis prediction: biomarkers combined in a bayesian approach[J]. Int J Mol Sci, 2025, 26(15): 7379.
20. Khuchua E, Didbaridze T, Ormotsadze G, et al. Evaluating the diagnostic and prognostic value of interleukin-6 (IL-6) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in systemic inflammatory response syndrome (SIRS) and sepsis in adults[J/OL]. Cureus, 2024, 16(11): e73310. DOI: 10.7759/cureus.73310.
21. Gibot S, Lafon T, Jacquin L, et al. Soluble TREM-1 plasma concentration predicts poor outcome in COVID-19 patients[J]. Intensive Care Med Exp, 2023, 11(1): 51.
22. Matos AO, Dantas PHDS, Silva-Sales M, et al. TREM-1 isoforms in bacterial infections: to immune modulation and beyond[J]. Crit Rev Microbiol, 2021, 47(3): 290-306.
23. Weiss G, Lai C, Fife ME, et al. Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors[J]. Mucosal Immunol, 2017, 10(4): 1021-1030.
24. Eman R, Mona M. Saber N, et al. TREM-1 receptor: a key player in inflammatory diseases[J]. Curr Mol Pharmacol, 2026, 19(1): 41-47.

West China Medical Journal

Value of peripheral blood soluble triggering receptor expressed on myeloid cells-1 and myeloid cell membrane-bound triggering receptor expressed on myeloid cells-1 in disease stratification of sepsis

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