1-16岁儿童乙肝疫苗接种后抗体水平变化规律分析及乙肝病毒母婴传播免疫逃逸机制探讨

发布时间：2018-04-10 03:23

本文选题：乙型肝炎病毒　切入点：疫苗　出处：《重庆医科大学》2017年硕士论文

【摘要】：第一部分1-16岁儿童乙肝疫苗接种后抗体水平变化规律分析目的:接种乙肝疫苗是目前预防乙型肝炎病毒感染(Hepatitis B Virus,HBV)最有效的方法,乙肝疫苗接种政策的实施显著降低了我国一般人群HBV感染率。这部分旨在分析1-16岁住院儿童婴幼儿期乙肝疫苗接种后抗体水平随年龄增长变化规律,评估接种加强针的必要性。方法:根据重庆医科大学附属儿童医院((Children’s Hospital of Chongqing Medical University,CHCMU)临床检验中心对93,326名1-16岁住院儿童乙肝标志物包括乙肝表面抗体(Hepatitis B Surface Antibody,HBs Ab),乙肝表面抗原(Hepatitis B Surface Antigen,HBs Ag)和乙肝核心抗体(Hepatitis B core Antibody HBc Ab)的检查结果,分析anti-HBs滴度变化规律及HBs Ag和HBc Ab的携带率。结果:93326名1-16岁住院儿童中HBs Ag和HBc Ab携带率分别为0.48%和4.05%。保护性抗体水平比例表现出先下降后上升的趋势,1岁年龄组血清保护率最高(90.31%),8岁年龄组最低(45.29%);所有年龄组儿童保护性抗体水平比例在45.29%-63.33%之间除1-3岁年龄组外(90.31%,83.95%和71.82%);绝大部分年龄组中高等抗体反应者比例在5.03%-10.56%之间;所有年龄组中没有发生血清转换的比例在3.33%-25.79%之间;男女之间抗体水平无显著统计学差异(p0.05)。有明确再接种史儿童抗体几何平均滴度(Geometric Mean Titers,GMT)显著高于不清楚是否有再接种及无再接种史儿童,前者与后两者相比均具有显著统计学差异(p0.0001),不清楚是否有再接种史儿童GMT也显著高于无再接种史儿童抗体水平(p0.05)。结论:我们通过大样本连续年龄段对出生后在婴幼儿期完成初次免疫接种的儿童调查研究发现1-16岁儿童总体抗体保护率为67.10%,1-8岁年龄组儿童中保护性抗体水平比例从90.31%下降至45.29%,而9-15岁年龄组中其抗体阳性率又从45.46%上升至63.33%,高等抗体水平者比例在大部分年龄组中保持相对稳定,没有表现出明显的下降或上升。接种加强针会显著增加抗体浓度,对没有发生抗体血清转换者建议再接种加强针,尤其是这些在学校住宿或者家庭成员中有HBs Ag携带者的儿童。第二部分乙肝病毒母婴传播免疫逃逸机制初步探讨目的:母婴传播是乙肝病毒最主要的传播方式,这部分主要探讨母亲为HBs Ag携带者所生新生儿在主被动免疫后仍然发展为慢性感染的高危因素,为进一步控制乙肝病毒母婴传播(Mother to Child Transmission,MTCT)提供参考。方法:收集母亲及孩子均携带HBs Ag、母亲携带HBs Ag而孩子健康和母亲及孩子均健康的母亲血液提取RNA,RNA经逆转录为c DNA后通过RT2 Profiler PCR Array和Affymetrix Prime View Human Gene Expression Array筛选具有显著差异表达基因。结果:参与固有免疫反应的84种关键基因筛查中共有11个基因有差异表达,其中上调的有9个,下调的有2个。人表达谱芯片可检测的基因数有20000个,通过分析发现8种可能与HBV母婴传播相关的基因,其中有1个基因表现为上调,7个基因表现为下调。结论:筛选出的差异表达基因参与固有免疫反应、细胞信号传导、细胞迁移、血管生成、凋亡、癌症发生等多种生物过程,它们可能在乙肝病毒母婴传播中发挥重要作用,需更多标本验证这一结果并发现可能的机制。
[Abstract]:The first part of the 1-16 year old children after hepatitis B vaccination antibody changes analysis objective: hepatitis B vaccination is the prevention of hepatitis B virus infection (Hepatitis B, Virus, HBV) the most effective method, the implementation of hepatitis B vaccination policies significantly reduced the Chinese general population infection rate of HBV. This part aims at the analysis of 1-16 hospitalized children infant hepatitis B vaccine antibody level changes with age, the necessity to strengthen the assessment of vaccination needle. Methods: according to the children's Hospital Affiliated to Medical University Of Chongqing ((Children s Hospital of Chongqing Medical University ', CHCMU) clinical inspection center on the 93326 1-16 year old children hospitalized for hepatitis B markers including hepatitis B surface antibody (Hepatitis B Surface Antibody HBs, Ab), hepatitis B surface antigen (Hepatitis B Surface Antigen, HBs Ag) and hepatitis B core antibody (Hepatitis B core Antibody HB C Ab) test results, analysis the carrying rate variation of anti-HBs Ag and HBc Ab titer and HBs. Results: 93326 1-16 year old children hospitalized in HBs Ag and HBc Ab carrying rate were 0.48% and 4.05%. protective antibody levels in proportion showed upward trend after the first drop, 1 year old age group serum protection rate the highest (90.31%), 8 year old age group was the lowest (45.29%); all age groups of children protective antibody levels between the proportion of 45.29%-63.33% in addition to 1-3 years age group (90.31%, 83.95% and 71.82%); the vast proportion of higher antibody response in most age groups in 5.03% -10.56% among all age groups; no seroconversion the proportion between 3.33%-25.79%; there was no statistically significant difference in antibody levels between men and women (P0.05). A clear history of children's vaccination with geometric mean titers (Geometric Mean, Titers, GMT) is not clear whether there is no vaccination and was significantly higher than that of Vaccinated children, the former and the latter two were compared with significant statistical difference (P0.0001), do not know whether there re vaccination history children GMT is significantly higher than that of no vaccination history of children's antibody level (P0.05). Conclusion: we are using a large sample of children ages of continuous investigation was born after the completion of initial immunization in infant period the discovery of 1-16 year old children overall antibody protection rate was 67.10%, antibody levels decreased from 90.31% to 45.29% to protect the 1-8 age group of children, and the antibody positive rate of 9-15 year old age group and increased from 45.46% to 63.33%, the proportion of high antibody level remained relatively stable in most age groups, showed no obviously decreased or increased. Vaccination strengthen a needle will significantly increase in antibody concentration of no antibody seroconversion suggested to strengthen vaccination needle, especially those in the school or family members There are HBs Ag carriers. Second children escape mechanism part of maternal transmission of hepatitis B virus immune to investigate: maternal transmission is the main mode of transmission of hepatitis B virus, this part mainly discusses the mother HBs Ag carriers newboms still risk factors for chronic infection in active passive immunization, to further control the maternal fetal transmission of hepatitis B virus (Mother to Child Transmission, MTCT) to provide the reference. Methods: to collect the mother and children were carrying HBs Ag and Ag HBs, the mother carrying a child's health and health of mothers and their children are the mother's blood RNA was extracted by RNA reverse transcription of C DNA by RT2 Profiler PCR Array and Affymetrix Prime View Human Gene Expression Array were significant the differentially expressed genes. Results: the participation of the innate immune response of 84 key genes screening differential expression of 11 genes, including the 9, there are 2 people down. The expression can be detected by microarray gene number 20000, through the analysis of 8 types of mother to child transmission of HBV related genes, including 1 genes up-regulated and 7 genes were downregulated. Conclusion: genes involved in innate reaction differentially expressed the cell signal transduction, cell migration, angiogenesis, apoptosis, cancer and a variety of biological processes, they may play an important role in maternal fetal transmission of hepatitis B virus, need more samples to verify this result and find the possible mechanism.

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R186

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