Endotoxin Exposure Alters-Anti-Tetanus IgE in Infants

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.