重症与轻症登革热B细胞反应动态变化及差异  

Dynamic Changes and Differences of B-cell Responses between Severe Dengue Disease and Mild Dengue Fever

作　　者：李泽[1] 王茜茜[1] 温莺芬[1] 郭文靖 赵令斋[1] 洪文昕[1] 张复春[1] 庾蕾[1] LI Ze;WANG Qian-qian;WEN Ying-fen;GUO Wen-jing;ZHAO Ling-zhai;HONG Wen-xin;ZHANG Fu-chun;YU Lei(Guangzhou Eighth People′s Hospital,Guangzhou Medical University,Guangzhou 510060,China)

机构地区：[1]广州医科大学附属广州市第八人民医院,广东广州510060

出　　处：《中山大学学报（医学科学版）》2020年第2期300-305,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广州市健康医疗协同创新重大专项(201803040006)。

摘　　要：[目的]探讨登革病毒I型(DENV-1)感染时,机体B细胞和浆细胞随病程的动态变化及其与疾病严重性的关系,为重症登革热的早期预警或治疗提供可能依据.[方法]选择2014年9月至12月登革热住院病例62例,设轻症登革热组(DF,n=33)、重症登革热组(SD,n=29)及对照组(control,n=6).采用多色流式细胞技术分析患者急性期及极期的外周血中B细胞及浆细胞随病程的动态变化及其在重症和轻症组的差异.进一步通过系列样品分析同一感染者(包括轻症和重症各3例)浆细胞随病程的变化,并且观察登革病毒初次及二次感染时,B细胞及其亚群即初始B细胞、记忆B细胞和浆细胞的变化.[结果]重症组B细胞扩增明显高于轻症组(P=0.013),特别是在病程第5~6天(P=0.017,0.002).轻症组和重症组浆细胞与对照组相比均有明显的增殖(P=0.011,0.032),但轻症和重症两组间相比差异无统计学意义.同一感染者系列样品分析显示,轻症病例浆细胞在病程第7~8天达高峰,第10天基本恢复正常.重症病例在病程第7~9天达高峰,但在病程10 d后仍有一定量的增殖.对于轻症登革热,二次感染组表现出更明显的B细胞增殖、初始B细胞减少及记忆B细胞减少(P=0.028,0.010,0.037),但浆细胞变化未体现出差异.而对于重症登革热,在二次感染时仅初始B细胞明显减少(P=0.018).[结论]DENV-1血清型感染时轻症和重症登革热组B细胞反应呈现不同的趋势.宿主在病程早期B细胞的明显扩增以及浆细胞延迟反应可能与疾病严重性相关.【Objective】To find out the possible marker for early warning or therapeutic target of severe denguedisease,we studied B cell responses during natural dengue virus(DENV)infection and their association with diseaseseverity.【Methods】Sixty-two cases and their blood samples were collected from the patients hospitalized during Septem-ber to December in 2014 and three groups were designated as mild dengue(DF,n=33),severe dengue(SD,n=29)andcontrol group(Control,n=6). Multicolor flow cytometrywas used to analyze the dynamic changes of B cells and plas-mablasts in the peripheral blood of patients during the acute phase and the critical phase. The plasmablasts in a succes-sion of samplesfrom the same infected patients(including 3 mild and 3 severe cases)were further analyzed. We alsoobserved the changes of B cells and their subsets,including naive B cells,memory B cells and plasmablasts,duringprimary and secondary infections.【Results】The expansion of B cells in the severe group was significantly higher than thatin the mild group(P=0.013),especially on day 5 and day 6 after the symptom onset(P = 0.017 and 0.002,respectively).Compared with those in the control group,the plasmablasts in the mild and severe groups showed significant proliferation(P = 0.011 and 0.032,respectively),but no statistical difference was observed between these two groups. The analysis ofthe serial blood samples showed that the plasmablasts,in mild cases,peaked on day 7 and 8 and returned to baseline onday 10,whereas in the severe group,peaked on day 7 to 9,and still existed at a certain rate after day 10. In mild denguegroup,more proliferative B cells,less naive B cells and memory B cells were found in secondary infection than in primaryinfection(P = 0.028,0.010 and 0.037,respectively),but plasmablasts revealed no difference. In severe dengue group,only na?ve B cells significantly decreased in secondary infection(P = 0.018).【Conclusion】B cell responses betweenmild and severe dengue after DENV-1 infection present different trends. The si

关 键 词：登革热 B细胞 浆细胞 增殖变化 

分 类 号：R511[医药卫生—内科学]