外周血C3aR1及NETs表达水平对脓毒症性凝血病的预测价值

曹锐, 刘开勋, 胡丹, 齐共健

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (12) : 1259-1264.

PDF(526 KB)
HTML
PDF(526 KB)
HTML
中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (12) : 1259-1264. DOI: 10.7499/j.issn.1008-8830.2307109
论著·临床研究

外周血C3aR1及NETs表达水平对脓毒症性凝血病的预测价值

  • 曹锐, 刘开勋, 胡丹, 齐共健
作者信息 +

Value of the expression levels of complement-3a receptor 1 and neutrophil extracellular traps in predicting sepsis-induced coagulopathy

  • CAO Rui, LIU Kai-Xun, HU Dan, QI Gong-Jian
Author information +
文章历史 +

摘要

目的 研究补体C3a受体1(complement-3a receptor1, C3aR1)及中性粒细胞胞外诱捕网(neutrophil extracellular traps, NETs)对脓毒症性凝血病(sepsis-induced coagulopathy, SIC)的临床预测价值。 方法 前瞻性纳入2022年6月—2023年6月于徐州医科大学附属徐州儿童医院就诊的脓毒症患儿78例为研究对象,根据是否发生SIC分为SIC组(36例)和非SIC组(42例)。比较两组临床资料、C3aR1和NETs水平,分析SIC发生的相关因素。应用受试者操作特征曲线(receiver operating characteristic curve, ROC曲线)评估C3aR1及NETs对SIC的预测效能。 结果 SIC组C反应蛋白、白细胞介素(interleukin, IL)-6、IL-10、C3aR1及NETs水平高于非SIC组(P<0.05)。多因素logistic回归分析显示,C3aR1、NETs及IL-6升高与SIC发生密切相关(P<0.05)。ROC曲线分析显示,C3aR1联合NETs预测SIC的曲线下面积为0.913(P<0.05),高于C3aR1、IL-6的曲线下面积(P<0.05),与NETs的曲线下面积比较差异无统计学意义(P>0.05)。 结论 SIC患儿外周血中C3aR1及NETs表达水平显著升高,二者表达水平对预测SIC发生具有较高的临床价值。

Abstract

Objective To investigate the clinical value of complement-3a receptor 1 (C3aR1) and neutrophil extracellular traps (NETs) in predicting sepsis-induced coagulopathy (SIC). Methods A prospective study was conducted among 78 children with sepsis who attended Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from June 2022 to June 2023. According to the presence or absence of SIC, they were divided into two groups: SIC (n=36) and non-SIC (n=42) . The two groups were compared in terms of clinical data and the levels of C3aR1 and NETs. The factors associated with the occurrence of SIC were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the performance of C3aR1 and NETs in predicting SIC. Results Compared with the non-SIC group, the SIC group had significantly higher levels of C-reactive protein, interleukin-6 (IL-6), interleukin-10, C3aR1, and NETs (P<0.05). The multivaiate logistic regression analysis showed that the increases in C3aR1, NETs, and IL-6 were closely associated with the occurrence of SIC (P<0.05). The ROC curve analysis showed that C3aR1 combined with NETs had an area under the curve (AUC) of 0.913 in predicting SIC (P<0.05), which was significantly higher than the AUC of C3aR1 or IL-6 (P<0.05), while there was no significant difference in AUC between C3aR1 combined with NETs and NETs alone (P>0.05). Conclusions There are significant increases in the expression levels of C3aR1 and NETs in the peripheral blood of children with SIC, and the expression levels of C3aR1 and NETs have a high clinical value in predicting SIC.

关键词

脓毒症 / 脓毒症性凝血病 / 补体C3a受体1 / 中性粒细胞胞外诱捕网 / 儿童

Key words

Sepsis / Sepsis-induced coagulopathy / Complement-3a receptor1 / Neutrophil extracellular trap / Child

引用本文

导出引用
曹锐, 刘开勋, 胡丹, 齐共健. 外周血C3aR1及NETs表达水平对脓毒症性凝血病的预测价值[J]. 中国当代儿科杂志. 2023, 25(12): 1259-1264 https://doi.org/10.7499/j.issn.1008-8830.2307109
CAO Rui, LIU Kai-Xun, HU Dan, QI Gong-Jian. Value of the expression levels of complement-3a receptor 1 and neutrophil extracellular traps in predicting sepsis-induced coagulopathy[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(12): 1259-1264 https://doi.org/10.7499/j.issn.1008-8830.2307109

参考文献

1 Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3)[J]. JAMA, 2016, 315(8): 801-810. PMID: 26903338. PMCID: PMC4968574. DOI: 10.1001/jama.2016.0287.
2 Iba T, Levy JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation[J]. Anesthesiology, 2020, 132(5): 1238-1245. PMID: 32044801. DOI: 10.1097/ALN.0000000000003122.
3 Iba T, Nisio MD, Levy JH, et al. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey[J]. BMJ Open, 2017, 7(9): e017046. PMID: 28963294. PMCID: PMC5623518. DOI: 10.1136/bmjopen-2017-017046.
4 Abe T, Kubo K, Izumoto S, et al. Complement activation in human sepsis is related to sepsis-induced disseminated intravascular coagulation[J]. Shock, 2020, 54(2): 198-204. PMID: 31917735. DOI: 10.1097/SHK.0000000000001504.
5 Xie K, Kong S, Li F, et al. Bioinformatics-based study to investigate potential differentially expressed genes and miRNAs in pediatric sepsis[J]. Med Sci Monit, 2020, 26: e923881. PMID: 32575108. PMCID: PMC7331480. DOI: 10.12659/MSM.923881.
6 Sauter RJ, Sauter M, Reis ES, et al. Functional relevance of the anaphylatoxin receptor C3aR for platelet function and arterial thrombus formation marks an intersection point between innate immunity and thrombosis[J]. Circulation, 2018, 138(16): 1720-1735. PMID: 29802205. PMCID: PMC6202244. DOI: 10.1161/CIRCULATIONAHA.118.034600.
7 Schmidt CQ, Schrezenmeier H, Kavanagh D. Complement and the prothrombotic state[J]. Blood, 2022, 139(13): 1954-1972. PMID: 34415298. DOI: 10.1182/blood.2020007206.
8 Abrams ST, Morton B, Alhamdi Y, et al. A novel assay for neutrophil extracellular trap formation independently predicts disseminated intravascular coagulation and mortality in critically ill patients[J]. Am J Respir Crit Care Med, 2019, 200(7): 869-880. PMID: 31162936. PMCID: PMC6812439. DOI: 10.1164/rccm.201811-2111OC.
9 中华医学会儿科学分会急救学组, 中华医学会急诊医学分会儿科学组, 中国医师协会儿童重症医师分会. 儿童脓毒性休克(感染性休克)诊治专家共识(2015版)[J]. 中华儿科杂志, 2015, 53(8): 576-580. PMID: 26717653. DOI: 10.3760/cma.j.issn.0578-1310.2015.08.007.
10 Schmoch T, M?hnle P, Weigand MA, et al. The prevalence of sepsis-induced coagulopathy in patients with sepsis: a secondary analysis of two German multicenter randomized controlled trials[J]. Ann Intensive Care, 2023, 13(1): 3. PMID: 36635426. PMCID: PMC9837358. DOI: 10.1186/s13613-022-01093-7.
11 de Bont CM, Boelens WC, Pruijn GJM. NETosis, complement, and coagulation: a triangular relationship[J]. Cell Mol Immunol, 2019, 16(1): 19-27. PMID: 29572545. PMCID: PMC6318284. DOI: 10.1038/s41423-018-0024-0.
12 Hayakawa M, Yamakawa K, Saito S, et al. Nationwide registry of sepsis patients in Japan focused on disseminated intravascular coagulation 2011-2013[J]. Sci Data, 2018, 5: 180243. PMID: 30531950. PMCID: PMC6289115. DOI: 10.1038/sdata.2018.243.
13 van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis[J]. Immunity, 2021, 54(11): 2450-2464. PMID: 34758337. DOI: 10.1016/j.immuni.2021.10.012.
14 van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets[J]. Nat Rev Immunol, 2017, 17(7): 407-420. PMID: 28436424. DOI: 10.1038/nri.2017.36.
15 Mollnes TE, Huber-Lang M. Complement in sepsis-when science meets clinics[J]. FEBS Lett, 2020, 594(16): 2621-2632. PMID: 32621378. DOI: 10.1002/1873-3468.13881.
16 Wang Y, Liu W, Xu Y, et al. Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins[J]. Nat Chem Biol, 2023, 19(11): 1351-1360. PMID: 37169960. DOI: 10.1038/s41589-023-01339-w.
17 Thiam HR, Wong SL, Wagner DD, et al. Cellular mechanisms of NETosis[J]. Annu Rev Cell Dev Biol, 2020, 36: 191-218. PMID: 32663035. PMCID: PMC8499668. DOI: 10.1146/annurev-cellbio-020520-111016.
18 Varjú I, Longstaff C, Szabó L, et al. DNA, histones and neutrophil extracellular traps exert anti-fibrinolytic effects in a plasma environment[J]. Thromb Haemost, 2015, 113(6): 1289-1298. PMID: 25789443. DOI: 10.1160/TH14-08-0669.
19 Pieterse E, Rother N, Garsen M, et al. Neutrophil extracellular traps drive endothelial-to-mesenchymal transition[J]. Arterioscler Thromb Vasc Biol, 2017, 37(7): 1371-1379. PMID: 28495931. DOI: 10.1161/ATVBAHA.117.309002.
20 周利兵, 陈娇, 杜晓晨, 等. 探讨3种评分系统对儿童严重脓毒症预后的评估价值[J]. 中国当代儿科杂志, 2019, 21(9): 898-903. PMID: 31506150. PMCID: PMC7390254. DOI: 10.7499/j.issn.1008-8830.2019.09.011.
21 Propson NE, Roy ER, Litvinchuk A, et al. Endothelial C3a receptor mediates vascular inflammation and blood-brain barrier permeability during aging[J]. J Clin Invest, 2021, 131(1): 140966. PMID: 32990682. PMCID: PMC7773352. DOI: 10.1172/JCI140966.
22 Alsabani M, Abrams ST, Cheng Z, et al. Reduction of NETosis by targeting CXCR1/2 reduces thrombosis, lung injury, and mortality in experimental human and murine sepsis[J]. Br J Anaesth, 2022, 128(2): 283-293. PMID: 34893315. PMCID: PMC8792833. DOI: 10.1016/j.bja.2021.10.039.
23 鲁海艳, 张高峰, 方长太, 等. 血清sTM、IL-6、PCT、E-选择素对脓毒症患者并发凝血功能异常的预测价值[J]. 山东医药, 2020, 60(17): 64-66. DOI: 10.3969/j.issn.1002-266X.2020.17.018.
24 俞秋兴, 张勇, 杜鸿, 等. 脓毒症患者中性粒细胞胞外诱捕网的定量研究[J]. 中华实验外科杂志, 2021, 38(11): 2216-2218. DOI: 10.3760/cma.j.cn421213-20210331-00273.
25 Yamakawa K, Yoshimura J, Ito T, et al. External validation of the two newly proposed criteria for assessing coagulopathy in sepsis[J]. Thromb Haemost, 2019, 119(2): 203-212. PMID: 30593085. DOI: 10.1055/s-0038-1676610.

基金

徐州市科技计划项目(KC21180)。

PDF(526 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/