检验医学 ›› 2023, Vol. 38 ›› Issue (5): 466-474.DOI: 10.3969/j.issn.1673-8640.2023.05.011

• 论著 • 上一篇    下一篇

化脓性脑膜炎患儿外周血NKG2C和GZMB标记NK细胞亚群变化的临床意义

杨泽1, 谢丽丽2, 田静1, 许同同3, 周国庆4, 刘宝军5, 武慧慧1()   

  1. 1.山东第一医科大学第二附属医院输血科,山东 泰安 271000
    2.山东第一医科大学第二附属医院肾内科,山东 泰安 271000
    3.山东第一医科大学第二附属医院检验科,山东 泰安 271000
    4.山东第一医科大学第二附属医院神经内科,山东 泰安 271000
    5.山东第一医科大学第二附属医院放疗科,山东 泰安 271000
  • 收稿日期:2021-03-18 修回日期:2022-03-18 出版日期:2023-05-30 发布日期:2023-08-07
  • 通讯作者: 武慧慧,E-mail:huihuiwu0518@163.com
  • 作者简介:杨 泽,男,1986年生,硕士,主管技师,主要从事自然杀伤细胞的免疫学功能研究。
  • 基金资助:
    山东省中医药科技发展计划项目(20190358)

Change and significance of NKG2C and granzyme B labeled NK cell subsets in peripheral blood of children with purulent meningitis

YANG Ze1, XIE Lili2, TIAN Jing1, XU Tongtong3, ZHOU Guoqing4, LIU Baojun5, WU Huihui1()   

  1. 1. Department of Blood Transfusion,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,Shandong,China
    2. Department of Nephrology,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,Shandong,China
    3. Department of Clinical Laboratory,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,Shandong,China
    4. Department of Internal Medicine Neurology,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,Shandong,China
    5. Department of Radiotherapy,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,Shandong,China
  • Received:2021-03-18 Revised:2022-03-18 Online:2023-05-30 Published:2023-08-07

摘要:

目的 探讨化脓性脑膜炎(PM)患儿外周血自然杀伤细胞受体2C(NKG2C)和颗粒酶B(GZMB)标记自然杀伤(NK)细胞亚群的变化特征及其临床意义。方法 选取PM患儿52例(PM组),根据出院时的格拉斯哥临床结局评分(GOS)分为预后良好组(44例)和预后不良组(8例)。以非中枢感染性疾病患儿52例作为对照组。采用流式细胞术检测所有患儿治疗前和PM患儿治疗后的外周血NK细胞各亚群[NKG2C-γ-干扰素(IFN-γ)+、NKG2C+INF-γ+、NKG2C+INF-γ-、NKG2C-GZMB+、NKG2C+GZMB+、NKG2C+GZMB-]。收集所有患儿脑脊液常规指标[总蛋白(TP)、葡萄糖(Glu)、氯离子(Cl-)、白细胞(WBC)计数]和外周血常规指标[WBC计数、中性粒细胞百分比(NEUT%)、降钙素原(PCT)、高敏C反应蛋白(hs-CRP)]检测结果。采用Spearman相关分析评估各项指标之间的相关性。采用受试者工作特征曲线(ROC)评价各项指标诊断PM和判断预后的效能。结果 PM组治疗前NKG2C+、NKG2C-GZMB+、NKG2C+GZMB+和NKG2C+GZMB- NK细胞百分比均显著高于对照组(P<0.05),总NK细胞百分比显著低于对照组(P<0.05)。2个组均未检测到NKG2C-INF-γ+和NKG2C+INF-γ+ NK细胞。Spearman相关分析结果显示,NKG2C-GZMB+ NK细胞百分比与脑脊液WBC计数、TP和血清PCT呈正相关(r值分别为0.286、0.558、0.740,P<0.05),与脑脊液Glu呈负相关(r=-0.389,P<0.05)。NKG2C+GZMB+ NK细胞百分比与脑脊液WBC计数、TP和外周血WBC计数、血清PCT呈正相关(r值分别为0.509、0.539、0.549、0.577,P<0.05),与脑脊液Glu呈负相关(r=-0.391,P<0.05)。NKG2C+GZMB- NK细胞百分比与脑脊液Glu呈正相关(r=0.624,P<0.05),与脑脊液TP呈负相关(r=-0.328,P<0.05)。PM组治疗后总NK细胞百分比和绝对值均高于治疗前(P<0.05)。与治疗前比较,预后良好组治疗后NKG2C-GZMB+和NKG2C+GZMB+ NK细胞百分比降低(P<0.05),NKG2C+GZMB- NK细胞百分比升高(P<0.05);预后不良组治疗后NKG2C+GZMB+ NK细胞百分比升高(P<0.05)。ROC曲线分析结果显示,NKG2C-GZMB+ NK细胞百分比诊断PM的效能最高,曲线下面积(AUC)为0.980,最佳临界值为8.93%,敏感性为92.31%,特异性为98.08%;治疗后NKG2C+GZMB- NK细胞判断PM患儿预后不良的效能最高,AUC为0.989,最佳临界值为5.51%,敏感性为100.00%,特异性为97.73%。结论 外周血NKG2C-GZMB+ NK细胞对PM诊断有较好的价值,NKG2C+GZMB- NK细胞对PM的预后评估有较高的价值。

关键词: 自然杀伤细胞受体2C, 颗粒酶B, 自然杀伤细胞, 化脓性脑膜炎

Abstract:

Objective To investigate the change characteristics and clinical significance of natural killer cell receptor 2C(NKG2C) and granzyme B(GZMB) labeled natural killer(NK) cell subsets in peripheral blood of children with purulent meningitis(PM). Methods Totally,52 children with PM and 52 control children with non-central infectious diseases were enrolled. The children with PM were classified into good prognosis group(44 cases) and poor prognosis group(8 cases) according to the Glasgow Outcome Scale on discharge. NK cell subsets [NKG2C- gamma-interferon gamma(INF-γ)+,NKG2C+INF-γ+,NKG2C+INF-γ-,NKG2C-GZMB+,NKG2C+GZMB+,NKG2C+GZMB-] were determined by flow cytometry. The results of cerebrospinal fluid white blood cell(WBC) count,total protein(TP),glucose(Glu) and chlorine(Cl-),peripheral blood WBC count,the percentage of neutrophil(NEUT%),serum procalcitonin(PCT) and high-sensitivity C-reactive protein(hs-CRP) were collected as well. Spearman rank correlation test was used to analyze the correlations. Receiver operating characteristic(ROC)curves were established to evaluate the values of the indicators in the diagnosis and prognosis of PM. Results The levels of NKG2C+,NKG2C-GZMB+,NKG2C+GZMB+ and NKG2C+GZMB- in PM group were higher than those in control group(P<0.05),and total NK cell percentage was lower than that in control group(P<0.05). There was no NKG2C-INF-γ+ and NKG2C+INF-γ+ NK cell in the 2 groups. The percentage of NK2G-GZMB+ NK cells was positively correlated with cerebrospinal fluid WBC count,TP and serum PCT(r values were 0.286,0.558 and 0.740,P<0.05),and it was negatively correlated with cerebrospinal fluid Glu(r=-0.389,P<0.05). The percentage of NKG2C+GZMB+ NK cells was positively correlated with cerebrospinal fluid WBC count,TP,peripheral blood WBC count and serum PCT(r=0.509,0.539,0.549 and 0.577,P<0.05),and it was negatively correlated with cerebrospinal fluid Glu(r=-0.391,P<0.05). NKG2C+ GZMB- NK cell percentage was positively correlated to cerebrospinal Glu level(r=0.624,P<0.05),and it was negatively correlated to cerebrospinal TP(r=-0.328,P<0.05). The percentage and absolute value of total NK cells in PM group after treatment were higher than those before treatment(P<0.05). Compared with before treatment,the percentage of NKG2C-GZMB+ and NKG2C+GZMB+ NK cells in good prognosis group were decreased after treatment(P<0.05),while the percentage of NKG2C+GZMB- NK cells was increased(P<0.05). The percentage of NKG2C+GZMB+NK cells in poor prognosis group after treatment was increased(P<0.05). ROC curve analysis results showed that NKG2C-GZMB+ NK cell percentage had the highest diagnostic efficiency for PM,with the area under curve(AUC) of 0.980,the optimal cut-off value of 8.93%,the sensitivity of 92.31%,and the specificity of 98.08%. After treatment,NKG2C+GZMB- NK cells had the highest efficiency in predicting poor prognosis in children with PM,with the AUC of 0.989,the optimal cut-off value of 5.51%,the sensitivity of 100.00%,and the specificity of 97.73%. Conclusions NKG2C-GZMB+ NK cell subsets have a good value for the early diagnosis in children with PM. NKG2C+GZMB- NK cells have a certain clinical value for prognostic prediction of PM.

Key words: Natural killer cell receptor 2C, Granzyme B, Natural killer cell, Purulent meningitis

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