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: 6986235
• 负责人: Dennis R Ownby
• 金额: $ 51.6万
• 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/6986235
• 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，婴儿期的动物暴露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降低可能是由于内毒素接触增加。鉴于美国变应性疾病的患病率日益增加，了解更多关于环境内毒素暴露与随后的变应性疾病之间的关系非常重要。本应用的目的是评估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）反应降低有关的假设。本研究采用正在进行的WHEALS研究（AI/ES 50681，一项评估3000名多种族儿童出生队列的卫生假设的研究）的结构。在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，以及起居室/家庭活动室地板）。内毒素测量的地点、月份和家庭特征（例如，家中的动物）之间的关系将被检查。这些分析将更好地了解内毒素暴露的变化，以及来自某些地点的测量是否与IgE的发展更密切相关。该队列中的所有婴儿预计在2、4、6-7和15-18个月时接受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和24月龄时常见过敏原的IgE特异性外，还将采用Pharmacia CAP法测量破伤风类毒素的IgE特异性。将分析aT-IgE测量结果，以了解IgE的产生是否受到内毒素或动物暴露的影响。测量at - ige的重要优点是，大多数婴儿可能在同一年龄接受相同的破伤风免疫接种，许多婴儿会出现at - ige。标准化的破伤风免疫与高度可变和难以测量的天然过敏原暴露形成对比，后者会缓慢诱导IgE抗体。由于aT-IgE反应的诱导更为迅速和普遍，因此测量aT-IgE可以更密切地评估动物和内毒素暴露与IgE发展之间的关系。更紧密的时间关系应该使我们更清楚地了解早期环境暴露对变应性疾病发展的作用。