非EV-A71肠道病毒感染引起的手足口病患者细胞因子表达谱变化  

Changes of cytokine expression profile in patients with hand,foot and mouth disease caused by non-EV-A71 enteroviruses

作　　者：关恒云[1] 王春荣[1] 刘岚铮[1] 赵怀龙[1] 杨国樑[1] 成洪旗[1] Guan Hengyun;Wang Chunrong;Liu Lanzheng;Zhao Huailong;Yang Guoliang;Cheng Hongqi(Jinan Municipal Center for Disease Control and Prevention,Jinan 250021,China)

机构地区：[1]济南市疾病预防控制中心,济南250021

出　　处：《中华实验和临床病毒学杂志》2022年第5期557-563,共7页Chinese Journal of Experimental and Clinical Virology

基　　金：山东省医药卫生科技发展计划(2016WS0116)。

摘　　要：目的阐明济南市非EV-A71肠道病毒(enterovirus A71,EV-A71)感染引起的手足口病(hand,foot,and mouth disease,HFMD)患者细胞因子表达谱变化,寻找特征性的细胞因子。方法收集济南市2014—2017年非EV-A71感染HFMD患者急性期和恢复期双份血清,同时收集健康人血清作为对照组。采用Bio-plex液相芯片平台高通量同时检测27种细胞因子,使用GraphPad Prism和SPSS 22.0进行描述和统计分析。结果非EV-A71感染患者较健康对照组22种血清细胞因子发生显著改变,包括11种白细胞介素(interleukin,IL)、5种趋化因子(chemokines)、2种生长因子(growth factors)、粒细胞-集落刺激因子(granulocyte colony stimulating factor,G-CSF)、干扰素-γ(interferon-γ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colony stimulating factor,GM-CSF)。柯萨奇病毒A组16型(coxsackievirus A16,CV-A16)感染者急性期和恢复期分别有21种(秩均值17.06~19.00 pg/ml,5.50~8.80 pg/ml,P<0.05)、20种(秩均值16.41~19.00 pg/ml,5.50~9.90 pg/ml,P<0.05)细胞因子表达较健康对照组升高,GM-CSF(秩均值9.65 pg/ml,21.40 pg/ml,9.59 pg/ml,21.50 pg/ml,P<0.05)均较健康对照组表达降低。CV-A6感染患者急性期和恢复期分别有19种(秩均值11.92~13.50 pg/ml,5.50~6.45 pg/ml,P<0.05)和21种(秩均值12.00~13.50 pg/ml,5.50~6.40 pg/ml,P<0.05)细胞因子表达较健康对照组升高,GM-CSF仅急性期(秩均值5.00 pg/ml,10.60 pg/ml,P<0.05)较健康对照组表达降低。双份血清分析显示:CV-A16感染患者恢复期IL-6(22.79pg/ml,35.88 pg/ml)和IFNγ诱导蛋白-10(interferon-induced protein 10,IP-10)(793.56 pg/ml,2157.32 pg/ml)表达较急性期降低;CV-A6感染患者恢复期IL-7(3.13 pg/ml,1.165 pg/ml)、IL-15(27.84 pg/ml,16.005 pg/ml)和正常T细胞表达和分泌调节活化因子(regulated upon activation normal T cell expressed and secreted,RANTES)(22605.96 pg/ml,7040.90 pg/ml)较急性期表达反而升高。�Objective To elucidate the changes of cytokine expression profiles in hand,foot and mouth disease(HFMD)patients infected with non-EV-A71 enteroviruses in Jinan city,and explore the characteristics of cytokines expression.Methods The serum samples of acute and convalescent phases were collected from non-EV-A71 enterovirus-infected HFMD patients in Jinan from 2014 to 2017.The serum samples of healthy subjects were collected as control group.The Bio-plex liquid chip platform was used for high-throughput detection of 27 cytokines.GraphPad Prism and SPSS 22.0 were used for description and statistical analysis.Results Twenty-two serum cytokines significantly changed in non-EV-A71 infected patients,including 11 kinds of interleukin(IL),5 kinds of chemokines,2 kinds of growth factors,granulocyte colony stimulating factor(G-CSF),interferon-γ,tumor necrosis factor-α(TNF-α)and granulocyte-macrophage colony stimulating factor(GM-CSF).There were 21 kinds(mean ranks 17.06-19.00 pg/ml vs 5.50-8.80 pg/ml,P<0.05)and 20 kinds(mean ranks 16.41-19.00 pg/ml vs 5.50-9.90 pg/ml,P<0.05)of cytokines expression in acute stage and convalescent stage respectively were higher than those in healthy control group for coxsackievirus A16(CV-A16)infected patients,and GM-CSF expression(mean ranks 9.65 pg/ml vs 21.40 pg/ml,9.59 pg/ml vs 21.50 pg/ml,P<0.05)were both lower than those in healthy control group.For HFMD patients infected CV-A6,there were 19 kinds(mean ranks 11.92-13.50 pg/ml vs 5.50-6.45 pg/ml,P<0.05)and 21 kinds(mean ranks 12.00-13.50 pg/ml vs 5.50-6.40pg/ml,P<0.05)of cytokines expression with acute and convalescent stage respectively were higher than those in healthy control group.GM-CSF expression decreased only in acute phase(mean ranks 5.00 pg/ml vs 10.60 pg/ml,P<0.05)compared with healthy control group.Double serum analysis showed that interleukin 6(22.79pg/ml vs 35.88 pg/ml)and interferon-induced protein 10(IFNγ-induced protein 10)(793.56 pg/ml vs 2157.32 pg/ml)expression in patients with CV-A16 infection during convalescent

关 键 词：手足口病 肠道病毒 细胞因子 液相芯片 

分 类 号：R725.1[医药卫生—儿科]