结核菌感染和卡介苗接种抗体应答特征初步研究

发布时间：2018-04-29 12:53

本文选题：结核分支杆菌 + 卡介苗接种　；参考：《中国人民解放军军事医学科学院》2009年硕士论文

【摘要】： 据世界卫生组织统计,全球有超过三分之一的人口感染了结核分支杆菌(M. tuberculosis ,MTB),每年有200万人因结核病死亡。第4次全国结核病流调结果显示,我国有5.5亿人曾感染MTB,人群感染率为44.5%,现有活动性结核患者500万,每年新发132万结核病人。新发结核病例,大部分由于内源性复发,而不是外源性感染。因此,如何发现结核潜感染者,如何预测结核潜感染者的预后,并对那些活动性结核病危险性最大的潜感染者实施预防性抗痨治疗,是当今国际上结核病控制的重要战略和研究重点。研究不同状态结核病感染和卡介苗(Bacille Calmette-Guerin, BCG)接种对结核免疫应答的影响,涉及结核病免疫预防和治疗、结核疫苗研发、结核病血清学诊断、结核病流行病学监测和结核病临床治疗诸领域,不仅具有重要的学术研究价值,而且对于结核病流行病学调研及临床治疗亦具有重要的实际意义。结核菌能合成约4000种蛋白,其中多数蛋白具有免疫原性,加上多糖和脂多糖抗原,结核抗原种类、数量众多。本研究基于结核病临床治疗和实验室诊断现状,采用国内外已广泛应用于结核病血清学诊断的3种分支杆菌抗原,调查结核菌临床感染者(结核病患者)、结核菌亚临床感染者(潜感染者)和BCG接种者相应抗体应答水平及其变化特点。这3种结核分支杆菌抗原是:部分纯化蛋白衍生物(Purified protein derivation, PPD)、脂阿拉伯甘露聚糖(lipoarabinomannan, LAM)和38 kDa蛋白。新兵是一个身体素质高、年龄相对集中(18-19岁)、且以男性为主的群体。尽管入伍时经过严格体检,但新兵入伍半年后,仍有少数人被诊断为结核病。由于军队的生活和工作环境高度集中,任何散在的结核病例均有可能引发结核病暴发流行,对我军战斗力造成严重危害。如何有效发现和预防士兵结核病,是一个非常现实和紧迫的课题,其关键是如何发现新兵中的活动性结核病的潜感染者,并及早给予预防性抗痨治疗。目前检测结核潜感染的方法主要有结核菌素皮肤试验(tuberculin skin test, TST)和r-干扰素释放试验(IGRAS)。TST用于检测结核潜感染已有很长的历史,但其特异性差,特别是在结核病高发地区。IGRAS是近年来开发的检测结核潜感染新技术,用于检测结核潜感染不受卡介苗(BCG)接种的影响。但是,该方法不能区分活动性结核病与结核潜感染,检测结果(致敏T-细胞r-干扰素释放量)与潜感染者的预后无关,且受MTB感染时间制约。本研究根据新兵TST结果,对TST阴性新兵接种BCG后体液免疫的变化进行了监测;对TST强阳性新兵结核特异性抗体水平进行了调查;对TST强阳性和38 kDa蛋白抗体阳性的新兵进行了随访和信访,同时对各类结核病患者相应抗体应答水平及其变化进行了观察,并探讨结核病患者、高危结核潜感染者和BCG接种者的区别方法。本研究采用的3种结核分支杆菌抗原是:部分纯化蛋白衍生物(PPD)、脂阿拉伯甘露聚糖(LAM)和38 kDa蛋白。本研究首先对无卡痕、TST试验阴性新兵在接种BCG疫苗后对3种抗原的抗体应答进行了连续监测,发现:种卡新兵对抗原LAM和38 kDa蛋白不产生抗体应答;种卡后新兵血清PPD抗体水平持续升高,3个月达高峰,种卡后6个月PPD抗体滴度仍显著高于种卡前。结果表明,种卡1年内,PPD抗体血清学检测不适用于结核病的诊断,而采用抗LAM和抗38 kDa蛋白抗体检测通常不受种卡影响。 10395名新兵TST试验结果表明,有卡痕和无卡痕新兵TST试验阳性率分别为70.2%和24.9%,差异非常显著(P0.001);TST试验强阳性率的有卡痕(3.3%)和无卡痕新兵(2.5%)之间的差异亦有显著性(P0.05),但TST试验不能区分结核潜感染者和BCG接种者。对TST强阳性新兵抗体应答特征进行调查和随访结果表明,TST强阳性新兵LAM抗体检测均为阴性,38 kDa蛋白抗体有6例阳性,其中5例为无卡痕新兵。3个月随访发现,6例TST强阳性且38 kDa蛋白抗体阳性新兵中,有3例具有结核体征,且均为无卡痕新兵。1年信访结果发现,无结核体征TST强阳性、38 kDa蛋白抗体阳性新兵健康状况良好,而3例有结核体征新兵中,1年内有2例诊断为结核性胸膜炎,另1例因工作调动失去联系。上述结果表明:TST强阳性且38 kDa蛋白抗体阳性可用作新兵结核菌潜感染的指标;本研究结果提示:对TST强阳性且38 kDa蛋白抗体阳性新兵给予预防性抗痨治疗,是降低士兵结核病发病率和减少部队结核病暴发流行最有效、最经济的防疫措施。结核菌潜感染新兵抗LAM抗体应答呈阴性;PPD抗体应答不能用于结核菌潜感染鉴别。对接受化疗的结核病患者的免疫应答调查表明:在化疗作用下,结核患者PPD抗体应答呈现3种模式。模式1患者占66.6%,多为菌阳病人,患者接受化疗后,PPD抗体水平持续增高,平均在化疗后1.8月抗体水平达到最高值,滴度升至化疗前的2～3倍,然后缓慢降低。模式2患者中复治病例比率高,接受化疗后血清PPD抗体从较高浓度逐渐降低。模式3患者多为病灶小、痰菌阴性、化疗前抗体水平低的初治结核患者,接受化疗后PPD抗体水平无变化。临床资料表明,化疗后抗体水平显著升高的患者疗效好。总之,本研究比较了临床活动性结核病人、结核菌潜感染者和BCG接种者的抗体应答特征,明确了新兵、儿童和新学员人群的结核病血清学诊断方法;明确了新兵结核潜感染的诊断方法;提出了士兵结核病预防措施;对结核病患者抗体应答特点及其与疗效的关系进行了初步探讨。
[Abstract]:According to the World Health Organization , more than a third of the world ' s population has been infected with M . tuberculosis , and 2 million people die each year due to tuberculosis . The fourth national tuberculosis epidemic has shown that more than 500 million people in China have been infected , with a population infection rate of 44.5 % . New tuberculosis cases , mostly due to endogenous recurrence , are not exogenous infections . Therefore , it is important to find out how to predict the prognosis of patients with latent tuberculosis , and to implement preventive anti - tuberculosis treatment for those who have the greatest risk of active tuberculosis .

To study the effect of tuberculosis infection and BCG vaccination on the immune response of tuberculosis , and to the field of tuberculosis immune prevention and treatment , tuberculosis vaccine development , tuberculosis serologic diagnosis , tuberculosis epidemic monitoring and tuberculosis clinical treatment , not only has important academic research value , but also has important practical significance for the investigation of tuberculosis epidemiology and clinical treatment .

Mycobacterium tuberculosis can synthesize about 4000 kinds of proteins , most of them have immunogenicity , combined with polysaccharide and lipopolysaccharide antigen , tuberculosis antigen kinds and quantity . This study is based on the present situation of tuberculosis clinical treatment and laboratory diagnosis .

It is a very realistic and urgent task to detect the latent infection of tuberculosis , and it is a very realistic and urgent task to detect the latent infection of tuberculosis .

In this study , the changes of humoral immunity after BCG vaccination were monitored by new recruits , and the specific antibody level of anti - tuberculosis positive and 38 kDa protein antibodies was investigated .

The results showed that PPD antibody serologic test was not suitable for the diagnosis of tuberculosis after BCG vaccination . The results showed that PPD antibody serologic test was not suitable for the diagnosis of tuberculosis after BCG vaccination . The results showed that PPD antibody serologic test was not suitable for the diagnosis of tuberculosis in 1 year , but the detection of anti - LAM and anti - 38 kDa protein antibody was not normally affected by seed card .

The results of the 10395 new recruits showed that the positive rates were 70.2 % and 24 . 9 % , respectively , and the difference was very significant ( P 0 . 001 ) . There was also a significant difference between the positive rate of positive rate ( 3.3 % ) and the new recruits ( 2.5 % ) .

The results showed that the positive and 38 kDa protein antibody positive recruits were positive and the 38 kDa protein antibody positive recruits were the most effective and economical epidemic prevention measures . The results showed that the positive and 38 kDa protein antibody positive recruits were the most effective and economical epidemic prevention measures . The PPD antibody response could not be used for the identification of anti - LAM antibody response .

The results showed that PPD antibody response in patients with tuberculosis was 66.6 % .

In conclusion , this study compared the antibody response characteristics of patients with clinically active tuberculosis , Mycobacterium tuberculosis latent infection and BCG vaccination , defined the diagnostic methods of tuberculosis serologic in the population of recruits , children and new students , defined the diagnosis methods of new recruits ' TB latent infection , proposed the preventive measures of soldiers tuberculosis , and discussed the relationship between antibody response characteristics and curative effect of tuberculosis patients .

【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R52;R186

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