Endotoxin Exposure Alters Anti-Tetenus IgE in Infants

描述（由申请人提供）：最近的研究表明，婴儿期高水平的内毒素暴露与随后的过敏敏感性风险降低有关。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具有潜在的重要意义。本应用的目的是评估高水平的环境内毒素暴露与婴儿常规破伤风类毒素免疫后抗破伤风IgE反应降低有关的假设。本研究将利用正在进行的WHEALS研究的结构（AI/ES 50681，一项评估密歇根州底特律及其周边地区3000名多种族儿童出生队列的卫生假设的研究）。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（婴儿婴儿床旁边的地板，婴儿床，父母床，父母床旁边的地板和客厅/家庭活动室的地板）。内毒素将使用商业动力学鲎试剂测定。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家庭内内毒素暴露的变化，并允许评估来自某些地点的测量是否与改变的IgE产生更密切相关。该队列中的所有婴儿预计在2、4、6-7和15-18月龄时接受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个月和24个月大时常见过敏原的IgE特异性外，还将使用商业Pharmacia CAP测定法在相同的血液样本中测量破伤风类毒素的IgE特异性。将分析抗破伤风IgE测量，以了解IgE的产生是否受到内毒素暴露的影响。测量抗破伤风IgE的重要优点是，大多数婴儿可能在同一年龄接受相同剂量的所有免疫接种。标准化的破伤风免疫与高度可变和难以测量的自然过敏原暴露形成对比。与对其他过敏原的反应相比，抗破伤风IgE反应也可能在婴儿期更早地被测量到。

DESCRIPTION (provided by applicant): Recent studies have suggested that high levels of endotoxin exposure during infancy are associated with a reduced risk of subsequent allergic sensitivity. Learning more about the relationship between environmental endotoxin exposure and subsequent allergic disease is potentially important given the increasing prevalence of allergic diseases 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 responses following routine immunizations with tetanus toxoid in infancy. This study will utilize 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 in and around Detroit, MI). In home endotoxin assessements will be increased from 1 to 5 locations (the floor beside the infant's crib, the infant's bed, the parent's bed, the floor beside the parent's bed, and the floor in the living/family room) during both the 1 and 6-month home visits. Endotoxin will be measured using a commercial kinetic Limulus assay. Relationships between endotoxin measurements by location, month of year, and household characteristics (e.g., animals in the home) will be examined. These analyses will provide a better understanding of variations in endotoxin exposure within homes and allow an assessment of whether measurements from certain locations are more closely related to altered IgE production. All infants in this 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 in the same blood samples using the commercial Pharmacia CAP assay. The anti-tetanus IgE measurements will be analyzed to learn whether IgE production is influenced by endotoxin exposure. Important advantages of measuring anti-tetanus IgE are the likelihood that most infants will receive all immunizations with identical doses at the same ages. The well standardized tetanus immunizations contrast with the highly variable and difficult to measure exposures to natural allergens. Anti-tetanus IgE responses are also likely to be measureable much earlier in infancy than are responses to other allergens.