Arsenic (As) is a common environmental toxicant to which millions of people in the U.S. are exposed via contaminated drinking water. Arsenic has been linked to increased risk of infectious disease and, possibly, other manifestations of immune dysfunction but there is uncertainty about the mechanism and full scope of its potential immunotoxicities. Emerging evidence suggests that As may perturb T cell function, including both effector T cells and T regulatory cells (Treg), a subset of T cells identified by our laboratoy and others to play a critical role in suppressing inflammation. Moreover, many immunotoxicants have profound effects when exposure occurs during prenatal development of the immune system. Yet, there are few, if any, studies of the relation of prenatal As exposure with specific measures of immune function. We propose to assess the relation of in utero As exposure (measured via maternal pregnancy urine As) with immune function at birth and age 1 year. The study will build on prospectively collected exposure, biospecimen, and extensive covariate and health data available from an ongoing cohort study of pregnant women and their infants in New Hampshire. Our hypothesis is that there will be a link between in utero As exposure and immune dysfunction, including impaired T cell and Treg function (in cord blood and placenta), which can lead to decreased responses to vaccinations, and possibly, increased infant susceptibility to infection and atopy. To test these hypotheses we will determine whether in utero As exposure is associated with: 1) impaired T cell and Treg function in infant cord blood samples, and 2) decreased immune indicators of placental tolerance. Also, we will 3) conduct exploratory analyses of T cell and Treg function in umbilical cord blood as predictors of enhanced risk of infant infections and atopic disorders as assessed during the 1st year of life, and 4) test the feasibility of determining T cell function, vaccine response and IgE levels in 1 year olds and their relation to As. We have established a new interdisciplinary collaboration between a clinical-scientist investigator with expertise in immunity and environmental and perinatal epidemiologists to advance understanding of the relation of a common environmental contaminant, As, with alterations in immune function and related childhood diseases. If the aims of our study are met, the results will be the basis for a more in depth study to confirm and extend our work and to develop new strategies for biomonitoring of immune function. Moreover, our study can be used to identify remediable environmental risk factors for prevalent childhood conditions with substantial public health importance, including infectious and atopic diseases. !

Public Health Relevance

Our study will address the impact of in utero exposure to arsenic, a common environmental contaminant, on immune markers in umbilical cord blood and placental tissue and help inform whether As-related changes in these immune markers also affect the risk of childhood infectious and allergic diseases. Identifying remediable environmental risk factors for these highly prevalent conditions worldwide could have profound long term public health consequences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21ES020936-02
Application #
8511633
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Gray, Kimberly A
Project Start
2012-07-16
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$195,554
Indirect Cost
$40,044
Name
Dartmouth College
Department
Family Medicine
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Nadeau, Kari C; Li, Zhigang; Farzan, Shohreh et al. (2014) In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort. Clin Immunol 155:188-97