Endotoxin Exposure Alters-Anti-Tetanus IgE in Infants

描述(由申请人提供)：许多研究表明，在婴儿期接触动物可以降低儿童后期过敏和哮喘的风险。与动物接触相关的过敏风险的降低可能是由于内毒素暴露的增加。鉴于过敏性疾病在美国日益流行，更多地了解环境内毒素暴露与随后的过敏性疾病之间的关系是重要的。这项应用的目的是评估这样一种假设，即高水平的环境内毒素暴露将与破伤风类毒素免疫后抗破伤风IgE(AT-IgE)反应减少相关。这项研究利用了正在进行的WHEALS研究的结构(AI/ES 50681，一项在3,000名儿童的多种族出生队列中评估卫生假说的研究)。在为期1个月和6个月的家访期间，家庭内毒素评估将从1个地点增加到5个地点(婴儿的床和地板，父母的床和地板，以及客厅/家庭房间地板)。将检查按地点、月份和家庭特征(例如，家里的动物)进行的内毒素测量之间的关系。这些分析将更好地了解内毒素暴露的变化，以及某些地点的测量是否与IgE的发展更密切相关。队列中的所有婴儿预计在2、4、6-7和15-18个月大时接受DTaP(白喉、破伤风和无细胞百日咳)疫苗常规免疫。除了在6个月和24个月龄时检测常见过敏原的特异性IgE外，还将通过Pharmacia CAP试验检测破伤风类毒素的特异性IgE。将对at-IgE测量进行分析，以了解IgE的产生是否受到内毒素或动物暴露的影响。检测at-IgE的重要优点是，大多数婴儿在相同的年龄接受相同的破伤风疫苗接种，并且许多婴儿将发展为at-IgE。标准化的破伤风疫苗接种与高度可变和难以测量的自然变应原暴露形成鲜明对比，自然变应原缓慢地诱导IgE抗体。由于更快速和更普遍地诱导AT-IgE反应，测定AT-IgE可以更接近时间地评估动物和内毒素暴露与IgE发育之间的关系。更密切的时间关系应该会更清楚地理解早期环境暴露在过敏性疾病发展中的作用。

DESCRIPTION (provided by applicant): Many studies have suggested that animal exposure in infancy reduces the risk of allergy and asthma later in childhood. The reduced allergic risk associated with animal exposure may be due to increased endotoxin exposure. Learning more about the relationship between environmental endotoxin exposure and subsequent allergic disease is important given the increasing prevalence of allergic disease in the United States. The goal of this application is to evaluate the hypothesis that high levels of environmental endotoxin exposure will be associated with reduced anti-tetanus IgE (aT-IgE) responses following tetanus toxoid immunizations. This study utilizes the structure of the ongoing WHEALS Study (AI/ES 50681, a study to evaluate the hygiene hypothesis in a multi-racial birth cohort of 3000 children). Home endotoxin assessments will be increased from 1 to 5 locations (infant's bed and floor, parent's bed and floor, and living/family room floor) during both the 1 and 6-month home visits. Relationships between endotoxin measurements by location, month, and household characteristics (e.g., animals in the home) will be examined. These analyses will provide a better understanding of variations in endotoxin exposure and whether measurements from certain locations are more closely related to the development of IgE. All infants in the cohort are expected to receive routine immunizations with DTaP (diphtheria, tetanus and acellular pertussis) vaccine at 2, 4, 6-7 and 15-18 months of age. In addition to measuring IgE specific for common allergens at 6 and 24 months of age, IgE specific for tetanus toxoid will be measured by Pharmacia CAP assay. The aT-IgE measurements will be analyzed to learn whether IgE production is influenced by endotoxin or animal exposures. Important advantages of measuring aT-IgE are the likelihood that most infants will receive identical tetanus immunizations at the same ages and that many will develop aT-IgE. The well standardized tetanus immunizations contrast with the highly variable and difficult to measure exposures to natural allergens, which slowly induce IgE antibodies. Because of the more rapid and more prevalent induction of aT-IgE responses, measuring aT-IgE allows a closer temporal evaluation of the relationships between animal and endotoxin exposure and IgE development. The closer temporal relationship should produce a clearer understanding of role of early environmental exposures on the development of allergic disease.