Developmental Exposure to Arsenic and Immune Function in Children

描述(申请人提供)：砷是一种常见的环境污染物，与人类包括癌症在内的不良健康后果有关。不太为人所知，但同样重要的是，有证据表明砷具有免疫毒性。这种污染物很容易通过胎盘，越来越多的证据表明，发育中的免疫系统对化学物质的伤害比成年人的免疫系统更敏感。然而，很少有研究研究早期接触这两种砷对儿童免疫功能的影响。因此，我们建议延长在孟加拉国招募的出生队列的随访时间，这些出生队列的早期接触砷。我们将利用存档的生物检验品来确定出生前和出生后早期接触砷的情况，并收集额外的血液样本，用于测量现在5岁儿童的疫苗抗体水平。这将使我们能够完成以下目标：1)确定产前砷暴露与传染病发病率的关系；2)确定产前砷暴露与人体病原体体液免疫发展的关系；3)探索产前砷与配对脐血-婴儿血中外周血白细胞免疫功能变化的关系。这项拟议研究的完成有望为儿童在发育的关键时期暴露于环境中的免疫调节效应提供新的见解。这一信息填补了我们在易感人群中暴露于与环境相关的浓度的砷的发育毒性知识方面的一个重要空白。这项研究的结果将具有临床意义，并有助于为可减轻儿童疾病负担的公共卫生干预措施提供信息。

DESCRIPTION (provided by applicant): Arsenic is a common environmental pollutant and associated with adverse health outcomes in humans including cancer. Less well known, but equally important, is evidence that arsenic is immunotoxic. This pollutant readily crosses the placenta and there is mounting evidence that the developing immune system is more sensitive to chemical insult than the immune system of adults. Yet few studies have examined the effect of early life exposure to either arsenic on children's immune functioning. We propose, therefore, to extend the follow-up of a birth cohort recruited in Bangladesh whose early life exposure to arsenic. We will utilize archived biospecimens to determine prenatal and early postnatal exposure to arsenic and collect additional blood samples that will be used to measure vaccine antibody levels in the children who are now 5 years of age. This will allow us to accomplish the following aims: 1) Determine the relationship between prenatal arsenic exposure and infectious diseases morbidity, 2) Determine the relationship between prenatal arsenic exposure and development of humoral immunity against human pathogens, and 3) Explore the association between prenatal arsenic and changes in immune profiles in peripheral leukocytes in paired cord-infant blood samples. Completion of the proposed research is expected to provide new insights into the immunomodulatory effects of environmental exposure during critical windows of development in children. This information addresses an important gap in our knowledge regarding the developmental toxicity of arsenic exposure at environmentally- relevant concentrations in susceptible populations. The outcomes from this research will be clinically relevant and help to inform public health interventions that can reduce the burden of disease in children.