Endotoxin Exposure Alters-Anti-Tetanus IgE in Infants

内毒素暴露会改变婴儿的抗破伤风 IgE

• 批准号: 6872686
• 负责人: Dennis R Ownby
• 金额: $ 39.41万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6872686
• 关键词: asthma; bacterial vaccines; biomarker; clinical research; clostridial tetanus; developmental immunology; disease /disorder proneness /risk; domestic animals; endotoxins; environmental exposure; hypersensitivity; immune response; immunoglobulin E; infant human (0-1 year); longitudinal human study; sample collection; tetanus toxoid

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.

描述（由申请人提供）：许多研究表明，婴儿期接触动物可降低儿童期过敏和哮喘的风险。与动物暴露相关的过敏风险降低可能是由于内毒素暴露增加。了解更多关于环境内毒素暴露和随后的过敏性疾病之间的关系是重要的，因为在美国过敏性疾病的患病率不断增加。本申请的目的是评价高水平环境内毒素暴露与破伤风类毒素免疫接种后抗破伤风IgE（aT-IgE）应答降低相关的假设。本研究利用正在进行的WHEALS研究（AI/ES 50681，一项在3000名儿童的多种族出生队列中评估卫生假设的研究）的结构。在1个月和6个月的家庭访视期间，家庭内毒素评估将从1个位置增加到5个位置（婴儿床和地板、父母床和地板以及起居室/家庭活动室地板）。按地点、月份和家庭特征（例如，家中的动物）进行检查。这些分析将更好地了解内毒素暴露的变化，以及某些位置的测量值是否与IgE的发生更密切相关。预计队列中的所有婴儿在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）疫苗的常规免疫接种。除了测量6月龄和24月龄时常见过敏原特异性IgE外，还将通过Pharmacia CAP测定法测量破伤风类毒素特异性IgE。将分析aT-IgE测量值，以了解IgE产生是否受内毒素或动物暴露的影响。测量aT-IgE的重要优点是大多数婴儿在相同年龄接受相同的破伤风免疫接种，并且许多婴儿将发展aT-IgE。标准化良好的破伤风免疫接种与高度可变且难以测量的天然过敏原暴露形成对比，天然过敏原缓慢诱导IgE抗体。由于aT-IgE应答的诱导更迅速和更普遍，因此测量aT-IgE可以更密切地评价动物和内毒素暴露与IgE形成之间的关系。更密切的时间关系应该产生一个更清晰的理解的作用，早期环境暴露的发展过敏性疾病。