[1]常正江,魏 倩,刘晓龙,等.新生儿脐血浆多种细胞因子水平检测与早发型新生儿败血症的相关性研究[J].现代检验医学杂志,2024,39(04):150-154.[doi:10.3969/j.issn.1671-7414.2024.04.027]
　CHANG Zhengjiang,WEI Qian,LIU Xiaolong,et al.Correlation between the Detection of Multiple Cytokine Levels in Neonatal Umbilical Cord Plasma and Early-onset Neonatal Sepsis[J].Journal of Modern Laboratory Medicine,2024,39(04):150-154.[doi:10.3969/j.issn.1671-7414.2024.04.027]
点击复制

新生儿脐血浆多种细胞因子水平检测与早发型新生儿败血症的相关性研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年04期
页码:
150-154
栏目:
论著
出版日期:
2024-07-15

文章信息/Info

Title:
Correlation between the Detection of Multiple Cytokine Levels in Neonatal Umbilical Cord Plasma and Early-onset Neonatal Sepsis
文章编号:
1671-7414（2024）04-150-05
作者:
常正江1; 魏 倩2; 刘晓龙2; 符兆英2; 陈美霓2; 何进伟2; 樊海燕3
（1. 延安市人民医院检验科，陕西延安716000；2. 延安大学医学院，陕西延安 716000；3. 榆林市第一医院检验科，陕西榆林 719000）
Author(s):
CHANG Zhengjiang1; WEI Qian2; LIU Xiaolong2; FU Zhaoying2; CHEN Meini2; HE Jinwei2; FAN Haiyan3
(1. Department of Clinical Laboratory, Yan’an People’s Hospital，Shaanxi Yan’an 716000，China; 2. School of Medicine, Yan’an University, Shaanxi Yan’an 716000，China; 3. Department of Clinical Laboratory, the First Hospital of Yulin, Shaanxi Yulin 719000，China)
关键词:
早发型新生儿败血症; 细胞因子; 脐带血
分类号:
R722.131；R392.11
DOI:
10.3969/j.issn.1671-7414.2024.04.027
文献标志码:
A
摘要:
目的 分析新生儿脐带血血浆多种细胞因子表达水平与早发型新生儿败血症(early-onset neonatal sepsis，EONS) 的相关性，旨在筛选出对新生儿早发型败血症有较大诊断价值的细胞因子。方法 以2021 年9 月～ 2023 年6 月在延安市人民医院出生的足月新生儿和早产新生儿（胎龄均≥ 32 周）310 例作为受试对象，根据临床体征、实验室检查和血培养结果分为三组：无败血症基础对照组、新生儿早发型败血症血培养阳性组和新生儿早发型败血症血培养阴性组；在受试对象出生后立即采集脐带血，测定血浆细胞因子IL-2，IL-4，IL-6，IL-9，IL-10，IL-21，IFN-γ 和TNF-α的表达水平，筛选出表达水平较高（关联性较高）的细胞因子，用受试者工作特征（receiver operating characteristic，ROC）曲线分析其单独检测和联合检测对新生儿早发型败血症诊断的特异度和敏感度。结果 患儿脐血浆上述8 种细胞因子中，IL-6，IL-9 和IL-21 浓度在新生儿早发型败血症血培养阳性组（392.6 ± 258.7 pg/ml，11.9 ± 7.5 pg/ml，29.1± 16.8 pg/ml）和新生儿早发型败血症血培养阴性组（353.8 ± 244.5 pg/ml，10.4 ± 6.3 pg/ml，27.7 ± 19.2 pg/ml）显著高于无败血症基础对照组（34.9 ± 25.1 pg/ml，5.9 ± 4.5 pg/ml，10.8 ± 10.1 pg/ml），差异具有统计学意义（t=23.961，20.732；15.174，17.824；22.466，21.193，均P<0.05），其中IL-6 浓度升高最为明显。新生儿早发型败血症血培养阳性组与新生儿早发型败血症血培养阴性组的细胞因子表达水平差异无统计学意义（t=0.276 ～ 3.377，均P>0.05）。ROC 曲线分析，IL-6，IL-9，IL-21 截断值分别为123.0 pg/ml，3.60 pg/ml 和6.00 pg/ml，IL-6，IL-9 和IL-21 单独检测ROC曲线下面积分别为0.876（95% CI：0.786 ～ 0.955），0.782（95% CI：0.667 ～ 0.875）和0.825（95% CI：0.737 ～ 0.913），三种细胞因子联合检测，ROC 曲线下面积为0.930（95% CI：0.875 ～ 0.997），IL-6，IL-9 和IL-21 联合检测能显著地提高检测的特异度和敏感度，差异具有统计学意义（Z=2.137，2.391，2.257，均P<0.05）。新生儿早发型败血症血培养阳性组与新生儿早发型败血症血培养阴性组的细胞因子表达水平差异均无统计学意义（t=0.276 ～ 3.377，均P>0.05）。结论 新生儿早发型败血症患儿脐血浆细胞因子IL-6，IL-9 和IL-21 显著升高，联合检测IL-6，IL-9 和IL-21 对新生儿早发型败血症有较好的诊断价值。
Abstract:
Objective To investigate correlation between the expression level of multiple cytokine levels in neonatal umbilical cord plasma and early-onset sepsis for screening out the cytokines with good diagnostic value for early-onset neonatal sepsis(EONS). Methods Full-term neonates and preterm neonates（Gestational age ≥ 32 weeks）of 310 cases between September 2021 and June 2023 were selected as study subjects. According to clinical signs, laboratory results and blood culture, these subjects were divided into 3 groups: control group without sepsis, EONS blood culture positive group and EONS blood culture negative group. Umbilical cord blood plasma of all subjects was collected within 72 hours after birth. The expression levels of cytokines IL-2，IL-4，IL-6，IL-9，IL-10，IL-21，IFN-γ and TNF-α were determined, and cytokines with high expression levels (high correlation) were screened out. Receiver operating characteristic (ROC) curve was used to analyze the specificity and sensitivity of the selected cytokines in the diagnosis of neonatal early-onset sepsis. Results Among the 8 cytokines mentioned above, the concentrations of IL-6, IL-9 and IL-21 in cord blood plasma of neonatal early-onset sepsis positive blood culture patients (392.6 ± 258.7pg/ml，11.9 ± 7.5pg/ml，29.1 ± 16.8 pg/ml) and negative blood culture patients (353.8 ± 244.5pg/ml，10.4 ± 6.3pg/ ml，27.7 ± 19.2pg/ml) were higher than those of the control group (34.9 ± 25.1pg/ml，5.9 ± 4.5pg/ml，10.8 ± 10.1pg/ml), with significant differences (t=23.961, 20.732; 15.174, 17.824; 22.466, 21.193, all P<0.01), and the increase of IL-6 concentration was the most obvious. ROC curve analysis (the cut-off values of IL-6, IL-9 and IL-21 :123.0 pg/ml, 3.60 pg/ml, 6.00 pg/ml, respectively)showed that the areas under the ROC curve for IL-6, IL-9 and IL-21 alone detection were 0.876 (95% CI: 0.786~0.955), 0.782 (95% CI: 0.667~0.875) and 0.825 (95% CI: 0.737~0.913), respectively. The area under the ROC curve for the combined detection of IL-6, IL-9 and IL-21 was 0. 930 (95% CI: 0.875~0.997). The combined detection of IL-6, IL-9 and IL-21 improved the specificity and sensitivity of the test than IL-6, IL-9 and IL-21 alone detection, and the differences were statistically significant (Z=2.137, 2.391, 2.257,all P<0.05). There was no significant difference in cytokine expression between positive blood culture and negative blood culture neonates with early-onset sepsis (t=0.276~3.377, all P>0.05). Conclusion The cytokines expression of IL-6, IL-9 and IL-21 in neonatal umbilical cord plasma of neonatal early-onset sepsis were increased. Combined detection of IL-6, IL-9 and IL-21 has good diagnostic value for early-onset neonatal sepsis.

参考文献/References:

[1] ODABASI I O, BULBUL A. Neonatal sepsis[J]. Sisli Etfal Hastanesi Tip Bulteni, 2020, 54(2): 142-158.
[2] MOLLOY E J, BEARER C F. Paediatric and neonatal sepsis and inflammation[J]. Pediatric Research, 2022, 91(2):267-269.
[3] ERSHAD M, MOSTAFA A, DELA CRUZ M, et al. Neonatal sepsis [J].Current Emergency and Hospital Medicine Reports, 2019, 7(3): 83-90.
[4] HINCU M A, ZONDA G I, STANCIU G D, et al. Relevance of biomarkers currently in use or research for practical diagnosis approach of neonatal early-onset sepsis [J]. Children (Basel), 2020, 7(12): 309.
[5] CANTEY J B, LEE J H. Biomarkers for the diagnosis of neonatal sepsis[J]. Clinics Perinatology, 2021, 48(2): 215-227.
[6] LEAL Y A, ?LVAREZ-NEMEGYEI J, LAVADORESMAY A I, et al. Cytokine profile as diagnostic and prognostic factor in neonatal sepsis [J]. Journal of Maternal-Fetal & Neonatal Medicine, 2019, 32(17): 2830-2836.
[7] LI Xia, SHAO Mi, ZENG Xiangjun, et al. Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy[J]. Signal Transduction and Targeted Therapy, 2021, 6(1): 367.
[8] LI Huihui, CHEN Chen, WANG Daowen. Inflammatory cytokines, immune cells, and organ interactions in heart failure[J]. Frontiers in Physiology, 2021, 12: 695047.
[9] YE Qing, DU Lizhong, SHAO Wenxia, et al. Utility of cytokines to predict neonatal sepsis[J]. Pediatric Research, 2017, 81(4): 616-621.
[10] FATTAH M A, OMER A F A, ASAIF S, et al. Utility of cytokine, adhesion molecule and acute phase proteins in early diagnosis of neonatal sepsis[J]. Journal of Natural Science, Biology and Medicine, 2017, 8(1): 32-39.
[11] LEHMANN J S, RUGHWANI P, KOLENOVIC M, et al. LEGENDplex?: bead-assisted multiplex cytokine profiling by flow cytometry[J]. Methods in Enzymology, 2019, 629: 151-176.
[12] 吴艳蓉, 梁跃波, 彭发兵, 等. 新生儿早发型败血症与晚发型败血症病原菌分布及炎性因子变化比较[J]. 现代医学, 2022, 50(1): 90-94. WU Yanrong, LIANG Yuebo, PENG Fabing, et al. Comparison of pathogen distribution and inflammatory factors in neonates with early-onset sepsis and late-onset sepsis [J]. Modern Medical Journal, 2022, 50(1): 90-94.
[13] 张江玲. 个性化干预模式对新生儿败血症的影响[J].中国妇幼保健, 2023, 38(6): 1129-1132. ZHANG Jiangling. Effect of individualized intervention mode on neonatal sepsis[J]. Maternal and Child Health Care of China, 2023, 38(6): 1129-1132.
[14] 陈明娟, 冯琳. 血清AT- Ⅲ , G6PD 检测对新生儿败血症早期诊断及预后评估的价值分析[J]. 蚌埠医学院学报, 2023, 48(2): 174-177. CHEN Mingjuan, FENG Lin. Value analysis of the serum levels of AT- Ⅲ and G6PD in the early diagnosis and prognosis of neonatal sepsis [J]. Journal of Bengbu Medical College, 2023, 48(2): 174-177.
[15] 吴小红, 颜海峰, 古裕鸟, 等. 感染标志物、炎症因子、血小板参数诊断新生儿早发型败血症的价值[J].中华医院感染学杂志, 2023, 33(7): 1090-1093. WU Xiaohong, YAN Haifeng, GU Yuniao, et al. Value of infectious markers, inflammatory factors and platelet parameters in the diagnosis of neonatal early-onset sepsis [J]. Chinese Journal of Nosocomiology, 2023, 33(7): 1090-1093.
[16] BERARDI A, TREVISANI V, DI CAPRIO A, et al. Timing of symptoms of early-onset sepsis after intrapartum antibiotic prophylaxis: can it inform the neonatal management? [J]. Pathogens, 2023, 12(4): 588.
[17] 康茹, 孟改利, 周雪红. 呼吸道感染患儿肠道菌群紊乱与Th17/Treg 及其分泌炎性细胞因子免疫平衡的相关性研究[J]. 现代检验医学杂志, 2021, 36(6): 95-100. KANG Ru, MENG Gaili, ZHOU Xuehong. Correlation analysis between intestinal flora disturbance and immune balance of Th17/Treg and its secretion of inflammatory cytokines children with respiratory tract infection [J]. Journal of Modern Laboratory Medicine, 2021, 36(6): 95-100.
[18] LIU Chunmei, FANG Chengzhi, HE Qi, et al.The value of interleukin-6 (IL-6) within 6 hours after birth in the prompt diagnosis of early-onset neonatal sepsis [J]. Translational Pediatrics, 2020, 9(5): 629-635.
[19] LI Zhaohui, SHENG Lei. Significance of dynamic evolution of TNF-α, IL-6 and intestinal fatty acidbinding protein levels in neonatal necrotizing enterocolitis [J]. Experimental and Therapeutic Medicine, 2018, 15(2): 1289-1292.
[20] WAN Jie, WU Yinqiu, JI Xiaoyun, et al. IL-9 and IL-9-producing cells in tumor immunity [J]. Cell Communication and Signaling, 2020, 18(1): 50.
[21] ROY S, RIZVI Z A, CLARKE A J, et al. EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells [J]. Nature Communications, 2021, 12(1): 3182.
[22] LONG Zhenyi, ZHOU Yifeng, YUAN Hao, et al. Expression and correlation of IgG4 and IL-21 in collagen-induced arthritis rats[J]. Journal of Inflammation Research, 2021, 14: 5051-5058.
[23] HEIM J, ALMANZAR G, SCHMALZING M, et al. Induction of IL-9 in peripheral lymphocytes of rheumatoid arthritis patients and healthy donors by Th17-inducing cytokine conditions [J], Frontiers Immunology, 2021, 12: 668095.
[24] LIN Xuan, YE Longyun, WANG Xu, et al. Follicular helper T cells remodel the immune microenvironment of pancreatic cancer via secreting CXCL13 and IL-21 [J]. Cancers (Basel), 2021, 13(15): 3678.
[25] HARPER J, HUOT N, MICCI L, et al. IL-21 and IFN-α therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques [J]. Nature Communications, 2021, 12(1): 2866.
[26] CAPITANI N, PATRUSSI L, BALDARI C T. Nature vs. Nurture: the two opposing behaviors of cytotoxic T lymphocytes in the tumor microenvironment [J]. International Journal of Molecular Sciences, 2021, 22(20): 11221.

相似文献/References:

[1]杨莉丽,江丹玲,陈文科,等.克罗恩病患者血清总 25羟维生素 D及细胞因子水平表达与疾病活动指数的相关性研究[J].现代检验医学杂志,2022,37(01):195.[doi:10.3969/j.issn.1671-7414.2022.01.040]
　YANG Li-li,JIANG Dan-ling,CHEN Wen-ke,et al.Correlation Study on Serum Total 25-Hydroxyvitamin D and Cytokine Levels with Disease Activity Index in Patients withCrohn’s Disease[J].Journal of Modern Laboratory Medicine,2022,37(04):195.[doi:10.3969/j.issn.1671-7414.2022.01.040]
[2]萧杏贤,刘　德,姜朝晖.AML不同疾病阶段患者T细胞耗竭及相关细胞因子表达水平实验研究[J].现代检验医学杂志,2022,37(03):138.[doi:10.3969/j.issn.1671-7414.2022.03.029]
　XIAO Xing-xian,LIU De,JIANG Zhao-hui.Experimental Study on T Cell Exhaustion and Related Cytokine Expression Levels in Patients with AML at Different Disease Stages[J].Journal of Modern Laboratory Medicine,2022,37(04):138.[doi:10.3969/j.issn.1671-7414.2022.03.029]
[3]邝 辉,尚 娟,努尔比叶,等.新疆维吾尔族静脉血栓患者Th17/Treg 细胞及相关细胞因子和细胞黏附分子整合素β 表达水平及临床意义[J].现代检验医学杂志,2022,37(05):28.[doi:10.3969/j.issn.1671-7414.2022.05.007]
　KUANG Hui,SHANG Juan,NUER·Biye,et al.Expression Levels and Clinical Significance of Th17/Treg Cells, Related Cytokines and Cell Adhesion Molecule Integrin β in Uygur Patients with Venous Thrombosis in Xinjiang[J].Journal of Modern Laboratory Medicine,2022,37(04):28.[doi:10.3969/j.issn.1671-7414.2022.05.007]
[4]李 蕊,杨 柳,周 磊,等.脓毒症患者外周血细胞因子，PCT和NLR表达水平及与临床预后价值研究[J].现代检验医学杂志,2024,39(01):67.[doi:10.3969/j.issn.1671-7414.2024.01.012]
　LI Rui,YANG Liu,ZHOU Lei,et al.Serum Cytokines, PCT and NLR Expression Levels and Their Diagnostic Value in Patients with Sepsis[J].Journal of Modern Laboratory Medicine,2024,39(04):67.[doi:10.3969/j.issn.1671-7414.2024.01.012]
[5]李彬钰a,马锡慧a,李 蕊a,等.老年新型冠状病毒感染患者外周血淋巴细胞亚群和多种细胞因子水平分析及其临床价值研究[J].现代检验医学杂志,2024,39(02):113.[doi:10.3969/j.issn.1671-7414.2024.02.021]
　LI Binyua,MA Xihuia,LI Ruia,et al.Analysis and Clinical Value of Lymphocyte Subsets and Various Cytokines of Peripheral Blood in Elderly Patients with COVID-19[J].Journal of Modern Laboratory Medicine,2024,39(04):113.[doi:10.3969/j.issn.1671-7414.2024.02.021]

备注/Memo

备注/Memo:
基金项目： 国家自然科学基金项目（41761100）：陕西省重点研发计划（2022SF-393）：陕西省教育厅科研计划项目（22JK0612）。
作者简介： 常正江（1984-），男，本科，主管检验师，研究方向：临床免疫学检验。
魏倩（1986-），女，硕士，实验员，研究方向：动物生理与药理，共同第一作者。
通讯作者：樊海燕（1972-），女，本科，副主任检验师，研究方向：医学检验与临床。
更新日期/Last Update: 2024-07-15