不同年龄段儿童手足口病免疫细胞变化特点的研究
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摘要
目的 分析不同年龄段儿童手足口病免疫细胞变化的特点,以期为儿童手足口病的预防诊治提供指导。方法 2015年1月-2018年1月收集1 090例不同年龄段手足口病(HMFD)患儿EDTA抗凝外周血,经破红、洗涤处理后分别加入CD3、CD4、CD8、CD19及CD16/CD56 5种荧光单抗对细胞进行标记,流式细胞仪对CD3+、CD4+、CD8+、CD19+及CD16+/CD56+五种免疫细胞含量进行分析。将患儿分为0～6个月、6个月<～5岁、5<～12岁3组,使用SPSS 19.0软件对3组患儿5种细胞含量构成比和升降幅度分别进行比较。结果 6个月<～5岁组患儿占总例数的89.1%,为HFMD高发组;该年龄段患儿CD3+(χ~2=9.824,P=0.007)、CD4+(χ~2=16.367,P<0.001)及NK(χ~2=8.666,P=0.013)细胞含量降低的比例, CD19+细胞(χ~2=13.867,P=0.001)含量增高的比例与其他年龄组患儿比较,差异均有统计学意义;另外,该年龄段患儿CD3+细胞(F=3.907,P=0.020)含量降低的幅度,CD19+细胞(F=9.952,P<0.001)含量升高的幅度较其他年龄组患儿比较,差异有统计学意义。结论 6个月<～5岁是HFMD的高发年龄段,该年龄段患儿免疫细胞的变化更为明显。细胞免疫功能指标的下降伴随CD19+细胞含量增高提示患儿病情急变,临床宜加强该年龄段患儿的免疫功能监控,调节免疫平衡,及早预防,从而改善患儿预后。
Objective To disclose the immunocytes variation feature of children with hand-foot-and-mouth disease(HFMD) in different age groups, in order to provide guidance for the prevention and treatment of HFMD. Methods Totally 1 090 HFMD children were enrolled in this study from January 2015 to January 2018, and their EDTA anticoagulation peripheral blood samples were collected. Fluorescence labeling monoclonal antibodies against CD3, CD4, CD8, CD19 and CD16/CD56 were separately used to mark WBCs after erythrocytolysis and purification. Flow cytometry was employed to analyze the immunocyte content. Children were divided into three groups, including 0～6 months, 6 months<-5 years old and 5<-12 years old. The constituent ratio and variations of content of CD3, CD4, CD8, CD19 and CD16/CD56 among different age groups were analyzed and compared by SPSS 19.0. Results HFMD was prevalent in children aged 6 months to 5 years(89.1%). There were significant differences on the constituent ratio of the decrease of CD3+(χ~2=9.824,P=0.007), CD4+(χ~2=16.367, P<0.001), NK(χ~2=8.666,P=0.013) and constituent ratio of the increase of CD19+(χ~2=13.867,P=0.001) cells between children aged 6 months to 5 years and other groups. Besides, the decrease level of CD3+ cells(F=3.907,P=0.020) and the increase level of CD19+ cells(F=9.952,P<0.001)were significantly different between children aged 6 months to 5 years and other groups. Conclusions HFMD is prevalent in children aged 6 months to 5 years, and the immunocyte variation is more obvious in this age group. Deficiency of cellular immunity accompanied with increase of CD19+ cells indicates the acute transformation of the disease. So more attention should be paid to immunologic monitoring and balance regulation, thereby improving prophylaxis and prognosis of these patients.
Objective To disclose the immunocytes variation feature of children with hand-foot-and-mouth disease(HFMD) in different age groups, in order to provide guidance for the prevention and treatment of HFMD. Methods Totally 1 090 HFMD children were enrolled in this study from January 2015 to January 2018, and their EDTA anticoagulation peripheral blood samples were collected. Fluorescence labeling monoclonal antibodies against CD3, CD4, CD8, CD19 and CD16/CD56 were separately used to mark WBCs after erythrocytolysis and purification. Flow cytometry was employed to analyze the immunocyte content. Children were divided into three groups, including 0～6 months, 6 months<-5 years old and 5<-12 years old. The constituent ratio and variations of content of CD3, CD4, CD8, CD19 and CD16/CD56 among different age groups were analyzed and compared by SPSS 19.0. Results HFMD was prevalent in children aged 6 months to 5 years(89.1%). There were significant differences on the constituent ratio of the decrease of CD3+(χ~2=9.824,P=0.007), CD4+(χ~2=16.367, P<0.001), NK(χ~2=8.666,P=0.013) and constituent ratio of the increase of CD19+(χ~2=13.867,P=0.001) cells between children aged 6 months to 5 years and other groups. Besides, the decrease level of CD3+ cells(F=3.907,P=0.020) and the increase level of CD19+ cells(F=9.952,P<0.001)were significantly different between children aged 6 months to 5 years and other groups. Conclusions HFMD is prevalent in children aged 6 months to 5 years, and the immunocyte variation is more obvious in this age group. Deficiency of cellular immunity accompanied with increase of CD19+ cells indicates the acute transformation of the disease. So more attention should be paid to immunologic monitoring and balance regulation, thereby improving prophylaxis and prognosis of these patients.
引文
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[12] Zhou Y,Shen C,Zhang C,et al.Yeast-produced recombinant virus-like particles of coxsackievirus A6 elicited protective antibodies in mice[J].Antiviral Res,2016,132:165-169.
[13] Shen C,Ku Z,Zhou Y,et al.Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections[J].Vaccine,2016,34(34):4025-4031.
[14] Chang LY,Huang LM,Gau SS,et al.Neurodevelopment and cognition in children after enterovirus 71 infection[J].N Engl J Med,2007,356(12):1226-1234.
[15] Chang LY,Hsiung CA,Lu CY,et al.Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71[J].Pediatr Res,2006,60(4):466-471.
[16] Plas DR,Rathmell JC,Thompson CB.Homeostatic control of lymphocyte survival:potential origins and implications[J].Nat Immunol,2002,3(6):515-521.
[17] Chang LY,Hsia SH,Wu CT,et al.Outcome of enterovirus 71 infections with or without stage-based management:1998 to 2002[J].Pediatr Infect Dis J,2004,23(4):327-332.
[18] Hsia SH,Wu CT,Chang JJ,et al.Predictors of unfavorable outcomes in enterovirus 71-related cardiopulmonary failure in children[J].Pediatr Infect Dis J,2005,24:331-334.
[19] 郑亚明,姜黎黎,嵇红.手足口病重症病例分析:基于全国手足口病监测试点数据[J].中华流行病学杂志,2017,38(6):759-762.
[20] 王燕霞.浅谈手足口病的防治[J].中国全科医学,2017,20(Suppl 2):158-160.
[2] Crabol Y,Pean P,Mey C,et al.A Prospective,comparative study of severe neurological and uncomplicated hand,foot and mouth forms of paediatric enterovirus 71 infections[J].Int J Infect Dis,2017,59:69-76.
[3] Xie J,Jiao Y,Qiu Z,et al.Significant elevation of B cells at the acute stage in enterovirus 71-infected children with central nervous system involvement[J].Scand J Infect Dis,2010,42(11-12):931-935.
[4] Lin YW,Chang KC,Kao CM,et al.Lymphocyte and antibody responses reduce enterovirus 71 lethality in mice by decreasing tissue viral loads[J].J Virol,2009,83(13):6477-6483.
[5] Wang SM,Lei HY,Huang KJ,et al.Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients:roles of cytokines and cellular immune activation in patients with pulmonary edema[J].J Infect Dis,2003,188(4):564-570.
[6] Wong SS,YiP CC,Lau SK,et al.Human enterovirus 71 and hand,foot and mouth disease[J].Epidemiol Infect,2010,138(8):1071-1089.
[7] 钟晓,张晓丽,郑振喜.CVA6型手足口病影响因素分析[J].热带医学杂志,2015,15(5):696-698.
[8] 程丽华,王艳,杨光.手足口病患者肠道病毒感染特征分析[J].中国病原生物学杂志,2018,31(2):199-201.
[9] Zhu FC,Liang ZL,Meng FY,et al.Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants[J].PLoS One,2012,7:e37206.
[10] Second J,Velter C,Cales S,et al.Clinicopathologic analysis of atypical hand,foot,and mouth disease in adult patients[J].J Am Acad Dermatol,2017,76(4):722-729.
[11] 李景良.重组柯萨奇A16病毒致病机理及候选疫苗对动物模型致死性保护机制[D].长春:吉林大学,2014.
[12] Zhou Y,Shen C,Zhang C,et al.Yeast-produced recombinant virus-like particles of coxsackievirus A6 elicited protective antibodies in mice[J].Antiviral Res,2016,132:165-169.
[13] Shen C,Ku Z,Zhou Y,et al.Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections[J].Vaccine,2016,34(34):4025-4031.
[14] Chang LY,Huang LM,Gau SS,et al.Neurodevelopment and cognition in children after enterovirus 71 infection[J].N Engl J Med,2007,356(12):1226-1234.
[15] Chang LY,Hsiung CA,Lu CY,et al.Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71[J].Pediatr Res,2006,60(4):466-471.
[16] Plas DR,Rathmell JC,Thompson CB.Homeostatic control of lymphocyte survival:potential origins and implications[J].Nat Immunol,2002,3(6):515-521.
[17] Chang LY,Hsia SH,Wu CT,et al.Outcome of enterovirus 71 infections with or without stage-based management:1998 to 2002[J].Pediatr Infect Dis J,2004,23(4):327-332.
[18] Hsia SH,Wu CT,Chang JJ,et al.Predictors of unfavorable outcomes in enterovirus 71-related cardiopulmonary failure in children[J].Pediatr Infect Dis J,2005,24:331-334.
[19] 郑亚明,姜黎黎,嵇红.手足口病重症病例分析:基于全国手足口病监测试点数据[J].中华流行病学杂志,2017,38(6):759-762.
[20] 王燕霞.浅谈手足口病的防治[J].中国全科医学,2017,20(Suppl 2):158-160.