Endotoxin Exposure Alters Anti-Tetenus IgE in Infants

内毒素暴露会改变婴儿的抗破伤风 IgE

• 批准号: 6767503
• 负责人: Dennis R Ownby
• 金额: $ 26万
• 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: 2004-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767503
• 关键词: active immunization; allergens; bacterial vaccines; clinical research; clostridial tetanus; cytokine; developmental immunology; domestic animals; dust; endotoxins; environmental exposure; human subject; immune response; immunoglobulin E; immunologic assay /test; interferon gamma; interleukin 4; monoclonal antibody; pregnancy; sample collection; tetanus toxoid

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.

描述（由申请人提供）：最近的研究表明，婴儿期的高水平内毒素暴露与随后的过敏敏感性的风险降低有关。鉴于美国过敏性疾病的患病率日益增加，有关环境内毒素暴露与随后的过敏性疾病之间关系的更多信息可能非常重要。该应用的目的是评估以下假设：高水平的环境内毒素暴露将与婴儿期在婴儿期常规免疫后的抗tetanus igE反应降低有关。这项研究将利用正在进行的WHEALS研究的结构（AI/ES 50681，一项研究，用于评估密歇根州底特律及其周围3000名儿童的多种族性出生队列中的卫生假设）。在家庭中，内毒素的评估将从1和6个月的房屋访问期间从1个地点（婴儿婴儿床，婴儿床，父母的床，父母床旁边的地板，父母床旁的地板以及地板）增加到5个地点。内毒素将使用商业动力学利润分析进行测量。将检查按位置，月份和家庭特征（例如，家庭中的动物）测量的内毒素测量之间的关系。这些分析将更好地理解房屋内内毒素暴露的变化，并允许评估某些位置的测量是否与改变的IgE产生更紧密相关。预计该队列中的所有婴儿均以2,4、6-7和15-18个月大的DTAP（白喉，破伤风和细胞百日咳）疫苗进行常规免疫接种。除了测量6个月和24个月大的普通过敏原的IgE外，使用商业药物帽测定法在相同的血液样本中还测量了特异性破伤风毒素的IgE。将分析抗tetanus IgE测量值，以了解IgE产生是否受内毒素暴露的影响。测量抗tetanus igE的重要优势是大多数婴儿在同一时代接受所有相同剂量的免疫接收。良好的标准化破伤风免疫与高度可变且难以测量对天然过敏原的暴露形成对比。抗tetanus igE反应在婴儿期还比对其他过敏原的反应早得早得多。