Marks Guy B, Ng Kitty, Zhou Jie, Toelle Brett G, Xuan Wei, Belousova Elena G, Britton Warwick J
Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia.
J Allergy Clin Immunol. 2003 Mar;111(3):541-9. doi: 10.1067/mai.2003.171.
There are conflicting reports on the effect of BCG vaccination on the subsequent development of atopy and asthma. There are no data on the effects of neonatal BCG vaccination on cytokine responses of lymphocytes that are exposed in vitro to allergens.
We sought to test the hypothesis that neonatal BCG vaccination or, alternatively, evidence of an immunologic memory of this vaccination is associated with a reduced prevalence of allergic sensitization, asthma, eczema, and hay fever during childhood.
An historical cohort study was conducted among 7- to 14-year-old children who were born in 2 districts in Sydney, Australia, and whose mothers were born in southeast Asia. One district had routinely administered BCG vaccination to infants born to overseas-born mothers and the other had not. Eligible subjects were identified from birth registers. Consenting subjects completed questionnaires, performed spirometric and airway hyperresponsiveness testing, and had allergen skin prick testing and tuberculin skin testing. Blood was collected to measure total serum IgE levels and for in vitro lymphocyte culture in the presence of an extract of house dust mite, the dominant allergen in this region, and purified protein derivative of Mycobacterium tuberculosis (tuberculin). IL-4, IL-5, IL-10, and IFN-gamma were measured in the culture supernatant.
The cohort included 309 BCG-vaccinated subjects and 442 non-BCG-vaccinated subjects. BCG-vaccinated subjects did not have a lower rate of allergic sensitization than nonvaccinated subjects. However, among the subgroup of subjects with a family history of rhinitis or eczema, BCG vaccination was associated with a lower prevalence of current asthma (defined as recent wheezing plus airway hyperresponsiveness; relative risk, 0.46; 95% CI, 0.22-0.95). BCG vaccination was also associated with lower levels of allergen-stimulated IL-10 production in vitro. Among the BCG-vaccinated subjects, the 44 (14.3%) who had tuberculin skin test reaction sizes of 5 mm or greater and the 31 (18.3%) who demonstrated an in vitro IFN-gamma response to purified protein derivative of M tuberculosis did not have lower rates of allergic sensitization and, overall, did not have a lower prevalence of allergic disease than tuberculin skin test or IFN-gamma nonreactors.
We conclude that neonatal BCG vaccination has an effect on T-cell allergen responsiveness 7 to 14 years after vaccination and that among a subgroup of subjects with an inherited predisposition to allergic disease, this is associated with clinically relevant beneficial effects. The findings of this study encourage the view that external influences on the immune system in the neonatal period have consequences that extend into later childhood and influence the expression of asthma. Genetic factors are likely to modify the effect of those external factors.
关于卡介苗接种对特应性疾病和哮喘后续发展的影响，存在相互矛盾的报道。目前尚无关于新生儿卡介苗接种对体外暴露于过敏原的淋巴细胞细胞因子反应影响的数据。
我们试图验证以下假设，即新生儿卡介苗接种或这种疫苗接种的免疫记忆证据与儿童期过敏性致敏、哮喘、湿疹和花粉热患病率降低有关。
对出生于澳大利亚悉尼两个区、母亲出生于东南亚的7至14岁儿童进行了一项历史性队列研究。一个区对海外出生母亲所生婴儿常规接种卡介苗，另一个区未接种。从出生登记册中确定符合条件的受试者。同意参与的受试者完成问卷调查、进行肺功能和气道高反应性测试，并进行过敏原皮肤点刺试验和结核菌素皮肤试验。采集血液以测量总血清IgE水平，并用于在存在该地区主要过敏原屋尘螨提取物和结核分枝杆菌纯化蛋白衍生物（结核菌素）的情况下进行体外淋巴细胞培养。在培养上清液中测量白细胞介素-4（IL-4）、白细胞介素-5（IL-5）、白细胞介素-10（IL-10）和干扰素-γ（IFN-γ）。
该队列包括309名接种卡介苗的受试者和442名未接种卡介苗的受试者。接种卡介苗的受试者的过敏性致敏率并不低于未接种疫苗的受试者。然而，在有鼻炎或湿疹家族史的受试者亚组中，卡介苗接种与当前哮喘（定义为近期喘息加气道高反应性）的患病率较低有关（相对风险，0.46；95%可信区间，0.22 - 0.95）。卡介苗接种还与体外过敏原刺激的IL-10产生水平较低有关。在接种卡介苗的受试者中，但结核菌素皮肤试验反应大小为5毫米或更大的44名（14.3%）受试者和对结核分枝杆菌纯化蛋白衍生物表现出体外IFN-γ反应的31名（18.3%）受试者，其过敏性致敏率并不低，总体而言，其过敏性疾病患病率并不低于结核菌素皮肤试验或IFN-γ无反应者。
我们得出结论，新生儿卡介苗接种在接种后7至14年对T细胞过敏原反应性有影响，并且在有过敏性疾病遗传易感性的受试者亚组中，这与临床相关的有益效果有关。本研究结果支持这样一种观点，即新生儿期对免疫系统的外部影响会产生延伸至儿童后期并影响哮喘表达的后果。遗传因素可能会改变这些外部因素的作用。
