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，婴儿期高水平的内毒素暴露与随后过敏性敏感性风险降低相关。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可能是重要的，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婴儿期常规破伤风类毒素免疫接种后抗破伤风IgE应答降低相关的假设。本研究将利用正在进行的WHEALS研究（AI/ES 50681，一项旨在评估密歇根州底特律及其周边地区3000名儿童的多种族出生队列中的卫生假设的研究）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（婴儿床旁的地板、婴儿床、父母床、父母床旁的地板和客厅/家庭活动室的地板）。将使用市售动态鲎试剂测定内毒素。按地点、月份和家庭特征（例如，家中的动物）进行检查。这些分析将提供一个更好的了解家庭内毒素暴露的变化，并允许从某些位置的测量是否更密切相关的IgE生产的评估。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月龄和24月龄时常见过敏原特异性IgE外，还将使用市售Pharmacia CAP检测试剂盒测量相同血液样本中破伤风类毒素特异性IgE。将分析抗破伤风IgE测量值，以了解IgE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在相同年龄接受相同剂量的所有免疫接种的可能性。标准化的破伤风免疫接种与高度可变和难以测量的天然过敏原暴露形成鲜明对比。抗破伤风IgE反应也可能在婴儿期比对其他过敏原的反应早得多。