本文選題：EB病毒　切入點：先天感染　出處：《北京協(xié)和醫(yī)學院》2014年博士論文

【摘要】：EB (Epstein-Barr)病毒感染與一些腫瘤疾病有密切的病因?qū)W關系,如Burkitt淋巴瘤、鼻咽癌等。該病毒在人群中感染極其普遍,感染后可以終身攜帶病毒抗體標記,迄今無有效的疫苗可以預防。經(jīng)口唾液傳播是目前公認的EB病毒主要傳播途徑,但EB病毒能否通過宮內(nèi)、產(chǎn)道或乳汁垂直傳播目前仍不明確。在中國的非鼻咽癌高發(fā)區(qū)——北方地區(qū),對于嬰幼兒EB病毒感染的流行病學調(diào)查資料十分匱乏。本研究收集吉林當?shù)爻ＷD女妊娠晚期及其新生兒配對的血樣本,并對該樣本進行血清抗體、DNA水平的相關測定,掌握吉林地區(qū)妊娠晚期婦女及新生兒EB病毒感染狀況。通過母嬰檢測結果對比,尋找EB病毒垂直傳播的相關證據(jù)。為新生兒EB病毒感染篩查,改善EB病毒感染診治水平及EB病毒疫苗的研發(fā)提供科學依據(jù)。 研究共收集500對母嬰樣本,其中,母親留取血清1.5ml,新生兒針刺足底留取濾紙干血片1張。樣本進行酶聯(lián)免疫吸附試驗(ELISA),檢測EB病毒抗體VCA-IgG, NA-IgG, EA-IgG, VCA-IgM,統(tǒng)計產(chǎn)婦及新生兒的抗EB病毒抗體陽性率,并據(jù)抗體譜分類將母親區(qū)分為急性感染、既往感染和未感染三大類。此外,研究提取新生兒濾紙干血片DNA,采用實時熒光定量PCR方法檢測EB病毒DNA拷貝數(shù)。對母嬰臨床資料進行回顧,按胎齡、出生方式、喂養(yǎng)方式等不同層面統(tǒng)計EB病毒的感染狀況。運用統(tǒng)計學分析軟件SAS9.2進行統(tǒng)計處理,組間比較采用X2檢驗,P0.05有統(tǒng)計學意義。 研究結果顯示,500對符合設定要求的母嬰研究樣本中,產(chǎn)婦有468例(93.6%)樣本的抗體譜提示EB病毒感染,急性感染和既往感染分別有109例(21.8%)和359例(71.8%),產(chǎn)婦的EB病毒急性感染率在本地區(qū)存在季節(jié)差異,秋冬季的急性感染率(27.8%)高于春夏季(11.1%),差異具有統(tǒng)計學意義(P0.05)；新生兒樣本中,提示EB病毒既往感染的EBV-CA-IgG抗體及EBNA-IgG抗體分別有466例(93.2%)和392例(78.4%)；提示EB病毒急性感染的EB-EA-IgG抗體及EBV-CA-IgM抗體分別有26例(5.2%)和4例(0.8%)。EB病毒抗體結合EBV-DNA檢測結果分析,新生兒EB病毒感染率為0.4%；根據(jù)4種抗體的結果,伴隨胎齡增加,新生兒VCA-IgG抗體的陽性率呈現(xiàn)緩慢升高的趨勢,差異具有統(tǒng)計學意義(P0.05),在38周,VCA-IgG抗體陽性率首次超過90%,達到與成人相當?shù)乃健?母嬰成對抗體檢測結果對比方面,按出生方式區(qū)分,自然分娩出生的新生兒四種抗體的陽性率均略高于剖宮產(chǎn)的新生兒,但差異不具有統(tǒng)計學意義(P0.05)；按喂養(yǎng)方式區(qū)分,提示既往感染的EB-VCA-IgG抗體陽性率及該抗體母嬰陽性匹配率在母乳喂養(yǎng)組中均高于非母乳喂養(yǎng)組,差異均具有統(tǒng)計學意義(P0.05),表明EB病毒存在母乳的垂直傳播途徑。研究考慮了生產(chǎn)方式及喂養(yǎng)方式對新生兒EB病毒抗體的影響。通過母嬰成對結果對比,證明胎盤、乳汁等途徑對EB病毒抗體垂直傳播均會產(chǎn)生一定影響,進而影響新生兒的EB病毒感染狀態(tài)。 研究結果描繪2013年4月至12月吉林地區(qū)產(chǎn)婦及其新生兒EB病毒感染狀況。該地區(qū)產(chǎn)婦EB病毒的感染率與目前公認的我國正常成年人感染率基本持平；但仍高于西方發(fā)達國家。產(chǎn)婦及新生兒EB病毒感染的數(shù)據(jù)在東北地區(qū)是第一次獲得,既往無比較先例,可以作為基線數(shù)據(jù),供今后研究參考。 在500份新生兒研究樣本中,EB病毒DNA弱陽性樣本2例,占0.4%,低于抗體譜的陽性率。由于實時熒光定量PCR方法檢測EB病毒DNA拷貝數(shù)僅在病毒活躍復制時才能檢測到,在以無癥狀的病毒攜帶者為主的正常新生兒中進行篩查,其對病毒感染狀態(tài)提示意義較為有限,需結合抗體譜及臨床信息具體分析。 濾紙干血片法檢測新生兒EB病毒抗體及DNA,彌補了傳統(tǒng)方式的不足,為未來擴大EB病毒感染篩查及開展新生兒EB病毒感染早期診斷提供了借鑒。
[Abstract]:Epstein - Barr virus ( EBV ) infection is closely related to some tumor diseases , such as Burkitt ' s lymphoma , nasopharyngeal carcinoma , etc . The virus is very common in the population and can carry virus antibody label for a lifetime after infection .

A total of 500 pairs of maternal and infant samples were collected from mother to infant . The positive rates of EB virus were detected by ELISA . The positive rates of EB virus were detected by ELISA . The results were analyzed by means of real - time fluorescence quantitative polymerase chain reaction ( RT - PCR ) , and the number of EB virus infection was analyzed by means of real - time fluorescence quantitative PCR .

The results showed that there were 468 cases ( 93.6 % ) of maternal and infant research samples which met the requirements of the setting , and there were 109 cases ( 21 . 8 % ) and 359 cases ( 71.8 % ) respectively . The acute infection rate of EB virus in the pregnant women was higher than that in the spring and summer ( 11.1 % ) , and the difference was statistically significant ( P0.05 ) .
The EBV - CA - IgG antibody and EBNA - IgG antibody of EBV - CA - IgG and EBNA - IgG were detected in 466 cases ( 93.2 % ) and 392 cases ( 78.4 % ) respectively .
The EBV - EA - IgG and EBV - CA - IgM antibodies were detected in 26 ( 5.2 % ) and 4 ( 0.8 % ) of EBV - CA - IgM antibodies , respectively . EBV - DNA detection results showed that the rate of EB virus infection was 0.4 % .
According to the results of four kinds of antibodies , the positive rate of the positive rate of IgG antibody of the newborn was increased slowly with the increase of the gestational age ( P0.05 ) . The positive rate of IgG antibody was over 90 % for the first time in 38 weeks , and reached the level corresponding to the adult .

The positive rates of four kinds of antibodies were slightly higher than those in cesarean section , but the difference was not statistically significant ( P0.05 ) .
The positive rate of Epstein - Barr virus ( EB ) and positive rate of maternal and infant positive rate of EB virus in breast feeding group were higher than that of non - breast feeding group ( P0.05 ) .

The results of the study depict the status of maternal and neonatal EB virus infection in Jilin area from April to December 2013 . The infection rate of maternal EB virus in the region is basically the same as that of the currently recognized normal adult infection rate in China ;
However , it is still higher than that of Western developed countries . The data of EB virus infection in maternal and newborn babies is the first time to be obtained in the north - east region and has no previous comparative precedent , which can be used as baseline data for future research and reference .

The positive rate of EB virus DNA was 0 . 4 % , which was lower than the positive rate of anti - EBV DNA in 500 newborn samples . The detection of EB virus DNA copy number was only detected by real - time fluorescence quantitative PCR .

Filter paper dry blood slice method detects EB virus antibody and DNA of newborn , makes up for the shortage of traditional methods , provides reference for the future expansion of EB virus infection screening and the early diagnosis of neonatal EB virus infection .

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R714.7

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本文編號：1684601