淋巴细胞亚群失衡与EV71型手足口病重症化的相关性

doi:10.3877/cma.j.issn.1674-1358.2017.02.011

中华实验和临床感染病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (02) : 156 -161. doi: 10.3877/cma.j.issn.1674-1358.2017.02.011

临床论著

淋巴细胞亚群失衡与EV71型手足口病重症化的相关性

王军¹, 邓慧玲¹, 袁娟¹, 张玉凤², 李亚萍³, 李梅³, 王文俊³, 高宁³, 党双锁³^,^†(

)

^1. 710004　西安市，西安交通大学第二附属医院感染科；710003　西安市，西安市儿童医院感染二科
^2. 710003　西安市，西安市儿童医院感染二科
^3. 710004　西安市，西安交通大学第二附属医院感染科

收稿日期:2016-07-04 出版日期:2017-04-15
通信作者: 党双锁
基金资助:
西安交通大学重大科研自助项目(No.YJ(ZDJH)201301); 陕西省科技统筹重点产业创新链工程计划项目(No. 2016KTZDSF02-04); 西安市科学技术局医疗卫生研究项目(No. 2016052SF/YX08)

Correlation between the unbalanced lymphocyte subsets and the aggravation condition of hand, foot and mouth disease with EV71 infection

Jun Wang¹, Huiling Deng¹, Juan Yuan¹, Yufeng Zhang², Yaping Li³, Mei Li³, Wenjun Wang³, Ning Gao³, Shuangsuo Dang³^,^†()

^1. Department of Infectious Diseases, the Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an 710004, China; Department of Infectious Diseases, Xi’an Children’s Hospital, Xi’an 710003, China
^2. Department of Infectious Diseases, Xi’an Children’s Hospital, Xi’an 710003, China
^3. Department of Infectious Diseases, the Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an 710004, China

Received:2016-07-04 Published:2017-04-15
Corresponding author: Shuangsuo Dang

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引用本文：

王军, 邓慧玲, 袁娟, 张玉凤, 李亚萍, 李梅, 王文俊, 高宁, 党双锁. 淋巴细胞亚群失衡与EV71型手足口病重症化的相关性[J/OL]. 中华实验和临床感染病杂志(电子版), 2017, 11(02): 156-161.

Jun Wang, Huiling Deng, Juan Yuan, Yufeng Zhang, Yaping Li, Mei Li, Wenjun Wang, Ning Gao, Shuangsuo Dang. Correlation between the unbalanced lymphocyte subsets and the aggravation condition of hand, foot and mouth disease with EV71 infection[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2017, 11(02): 156-161.

目的

研究EV71型手足口病患儿淋巴细胞亚群失衡与手足口病重症化之间的相关性。

方法

收集2013年4月至2015年10月间本院收治的EV71型手足口病患儿共496例，根据病情分为普通型组（220例）、重症组（191例）以及危重症组（85例）；选择同期本院门诊100例健康体检儿童为对照组。采取流式细胞仪检测各组患儿外周血T淋巴细胞（CD3⁺）、Th细胞（CD3⁺CD4⁺）、Tc细胞（CD3⁺CD8⁺）、NK细胞（CD16⁺56⁺）和B淋巴细胞（CD19⁺）数量及其所占淋巴细胞的百分比，并应用ELISA法测定各组细胞因子IL-6、IL-10、TNF-α和IFN-γ的血清浓度。

结果

淋巴细胞亚群CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺的百分比在对照组、普通型组、重症组和危重症组中逐渐降低；而CD19⁺则呈相反趋势；CD16⁺CD56⁺百分比在对照组、重症组、普通型组、危重症组中依次降低。各组淋巴细胞亚群差异具有统计学意义（F = 243.38、206.52、41.85、4.27、314.54，P均< 0.05），而组间比较中，除重症组和危重症组患儿CD3⁺CD4⁺、对照组和重症组以及普通型组和危重症组患儿CD16⁺CD56⁺差异无统计学意义外（P > 0.05），其余各组差异具有统计学意义（P均< 0.05）。细胞因子IL-6和IL-10在对照组、普通型组、重症组和危重症组中逐渐升高；TNF-α和IFN-γ在对照组、普通型组、重症组中逐渐升高，但在危重症组中却出现下降。各组细胞因子差异具有统计学意义（F = 55.32、75.47、416.37、321.31，P均< 0.05）；而组间多重比较中，差异亦具有统计学意义（P均< 0.05）。

结论

EV71型手足口病患儿存在细胞免疫功能紊乱和炎症因子失调；淋巴细胞亚群失衡可能为手足口病重症化的重要因素之一。

关键词: 手足口病, 肠道病毒71型, 免疫功能, 淋巴细胞亚群, 细胞因子

Objective

To investigate the correlation between the unbalanced lymphocyte subsets and the aggravation condition of children with EV71-assoicated hand, foot and mouth disease (HFMD).

Methods

Total of 496 patients with EV71-assoicated HFMD were collected in the hospital from April 2013 to October 2015, and were divided into the common group (220 cases), severe group (191 cases) and critical group (85 cases). While 100 healthy children who received checkup during the same period were recruited in the control group. The lymphocyte subsets in peripheral blood, including T lymphocytes (CD3⁺), Th cells (CD3⁺CD4⁺), Tc cells (CD3⁺CD8⁺), NK cells (CD16⁺56⁺) and B lymphocytes (CD19⁺) were detected by flowcytometry in terms of count and percentage in total lymphocytes. And the serum levels of IL-6, IL-10, TNF-α and IFN-γ were determined by ELISA.

Results

The percentages of such lymphocyte subsets as CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺ were decreased sequentially in the control group, and the common, severe and critical groups; and the oppositely sequential decline was indicated in the percentage of CD19⁺. The percentage of CD16⁺CD56⁺ was reduced sequentially in the control group, and the severe, common and critical groups. The lymphocyte subsets were significantly different among the patients in different groups (F = 243.38, 206.52, 41.85, 4.27, 314.54; all P < 0.05). In inter-group comparison, no significant difference of CD3⁺CD4⁺ was observed between the severe and critical groups (all P > 0.05), and no significant difference of CD16⁺CD56⁺ were observed between the control group and the severe group and also between the common and critical groups (all P > 0.05); a significant difference of the other subsets was indicated among the four groups (all P < 0.05). The levels of such cytokines as IL-6 and IL-10 were increased sequentially in the control group, and the common, severe and critical groups; the levels of TNF-α and IFN-γ were increased sequentially in the control group, the common and severe groups, but decreased in the critical group. The levels of the cytokines were significantly different among the four groups (F = 55.32, 75.47, 416.37, 321.31; all P < 0.05), a significant difference was also observed in multiple inter-group comparisons (all P < 0.05).

Conclusions

The children with EV71-assoicated HFMD had disordered cellular immune function and abnormal inflammatory factors. And the unbalanced lymphocyte subsets may play an important role in the aggravation condition in those with HFMD.

Key words: Hand, foot and mouth disease, Human enterovirus 71, Immune function, Lymphocyte subsets, Cytokines

表1 各组患儿外周血淋巴细胞亚群水平（±s，%）

组别	例数	CD3⁺	CD3⁺CD4⁺	CD3⁺CD8⁺	CD16⁺CD56⁺	CD19⁺
对照组	100	68.95±8.31	44.60±10.50	27.05±8.12	13.15±6.19	14.10±6.75
普通型组	220	59.50±9.72^a	29.65±8.68^a	22.05±10.79^a	11.20±5.62^a	21.65±9.21^a
重症组	191	44.72±10.58^ab	21.55±7.39^ab	17.92±6.41^ab	12.73±7.48^b	39.34±10.58^ab
危重症组	85	38.38±7.45^abc	19.57±5.42^ab	14.76±4.99^abc	10.57±6.79^ac	47.76±9.99^abc
F值		243.380	206.520	41.850	4.270	314.540
P值		< 0.001	< 0.001	< 0.001	0.005	< 0.001

表1 各组患儿外周血淋巴细胞亚群水平（±s，%）

组别	例数	CD3⁺	CD3⁺CD4⁺	CD3⁺CD8⁺	CD16⁺CD56⁺	CD19⁺
对照组	100	68.95±8.31	44.60±10.50	27.05±8.12	13.15±6.19	14.10±6.75
普通型组	220	59.50±9.72^a	29.65±8.68^a	22.05±10.79^a	11.20±5.62^a	21.65±9.21^a
重症组	191	44.72±10.58^ab	21.55±7.39^ab	17.92±6.41^ab	12.73±7.48^b	39.34±10.58^ab
危重症组	85	38.38±7.45^abc	19.57±5.42^ab	14.76±4.99^abc	10.57±6.79^ac	47.76±9.99^abc
F值		243.380	206.520	41.850	4.270	314.540
P值		< 0.001	< 0.001	< 0.001	0.005	< 0.001

表2 淋巴细胞亚群组间SNK-q检验结果

淋巴细胞亚群	对照组						普通型组				重症组
	普通型		重型组		危重型组		重症组		危重症组		危重症组
	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值
CD3⁺	11.66	< 0.01	29.21	< 0.01	30.83	< 0.01	22.24	< 0.01	24.61	< 0.01	7.23	< 0.01
CD3⁺CD4⁺	21.25	< 0.01	32.02	< 0.01	29.09	< 0.01	14.04	< 0.01	13.53	< 0.01	2.59	> 0.05
CD3⁺CD8⁺	6.96	< 0.01	12.43	< 0.01	14.00	< 0.01	7.01	< 0.01	9.59	< 0.01	4.07	< 0.01
CD16⁺CD56⁺	3.50	< 0.05	0.73	> 0.05	3.78	< 0.05	3.35	< 0.05	1.06	> 0.05	3.58	< 0.05
CD19⁺	9.37	< 0.01	30.63	< 0.01	34.18	< 0.01	26.80	< 0.01	30.63	< 0.01	9.67	< 0.01

表2 淋巴细胞亚群组间SNK-q检验结果

淋巴细胞亚群	对照组						普通型组				重症组
	普通型		重型组		危重型组		重症组		危重症组		危重症组
	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值
CD3⁺	11.66	< 0.01	29.21	< 0.01	30.83	< 0.01	22.24	< 0.01	24.61	< 0.01	7.23	< 0.01
CD3⁺CD4⁺	21.25	< 0.01	32.02	< 0.01	29.09	< 0.01	14.04	< 0.01	13.53	< 0.01	2.59	> 0.05
CD3⁺CD8⁺	6.96	< 0.01	12.43	< 0.01	14.00	< 0.01	7.01	< 0.01	9.59	< 0.01	4.07	< 0.01
CD16⁺CD56⁺	3.50	< 0.05	0.73	> 0.05	3.78	< 0.05	3.35	< 0.05	1.06	> 0.05	3.58	< 0.05
CD19⁺	9.37	< 0.01	30.63	< 0.01	34.18	< 0.01	26.80	< 0.01	30.63	< 0.01	9.67	< 0.01

表3 各组患儿细胞因子水平（±s，pg/ml）

组别	例数	IL-6	TNF-α	IFN-γ	IL-10
对照组	100	9.25±5.48	18.3±5.65	20.19±10.15	8.59±2.62
普通型组	220	16.38±7.59^a	20.6±10.24^a	45.07±12.31^a	18.31±5.61^a
重症组	191	20.21±9.71^ab	28.9±8.61^ab	69.22±18.61^ab	24.59±4.95^ab
危重症组	85	22.94±8.23^abc	14.5±3.04^abc	15.02±10.45^abc	32.15±8.57^abc
F值		55.320	75.470	416.370	321.310
P值		< 0.001	< 0.001	< 0.001	< 0.001

表3 各组患儿细胞因子水平（±s，pg/ml）

组别	例数	IL-6	TNF-α	IFN-γ	IL-10
对照组	100	9.25±5.48	18.3±5.65	20.19±10.15	8.59±2.62
普通型组	220	16.38±7.59^a	20.6±10.24^a	45.07±12.31^a	18.31±5.61^a
重症组	191	20.21±9.71^ab	28.9±8.61^ab	69.22±18.61^ab	24.59±4.95^ab
危重症组	85	22.94±8.23^abc	14.5±3.04^abc	15.02±10.45^abc	32.15±8.57^abc
F值		55.320	75.470	416.370	321.310
P值		< 0.001	< 0.001	< 0.001	< 0.001

表4 细胞因子组间SNK-q检验结果

指标	对照组						普通型组				重症组
	普通型		重型组		危重型组		重症组		危重症组		危重症组
	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值
IL-6	10.27	< 0.01	15.43	< 0.01	16.12	< 0.01	6.73	< 0.01	8.92	< 0.01	3.63	< 0.01
TNF-α	3.24	< 0.05	14.59	< 0.01	4.37	< 0.01	14.26	< 0.01	8.11	< 0.01	18.77	< 0.01
IFN-γ	20.63	< 0.01	39.72	< 0.01	3.50	< 0.01	24.42	< 0.01	23.53	< 0.01	41.57	< 0.01
IL-10	20.44	< 0.01	32.88	< 0.01	40.51	< 0.01	16.10	< 0.01	27.49	< 0.01	14.70	< 0.01

表4 细胞因子组间SNK-q检验结果

指标	对照组						普通型组				重症组
	普通型		重型组		危重型组		重症组		危重症组		危重症组
	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值	q值	P值
IL-6	10.27	< 0.01	15.43	< 0.01	16.12	< 0.01	6.73	< 0.01	8.92	< 0.01	3.63	< 0.01
TNF-α	3.24	< 0.05	14.59	< 0.01	4.37	< 0.01	14.26	< 0.01	8.11	< 0.01	18.77	< 0.01
IFN-γ	20.63	< 0.01	39.72	< 0.01	3.50	< 0.01	24.42	< 0.01	23.53	< 0.01	41.57	< 0.01
IL-10	20.44	< 0.01	32.88	< 0.01	40.51	< 0.01	16.10	< 0.01	27.49	< 0.01	14.70	< 0.01

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Correlation between the unbalanced lymphocyte subsets and the aggravation condition of hand, foot and mouth disease with EV71 infection

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Correlation between the unbalanced lymphocyte subsets and the aggravation condition of hand, foot and mouth disease with EV71 infection