Developmental Exposure to Arsenic and Immune Function in Children

描述（由申请人提供）：砷是一种常见的环境污染物，与包括癌症在内的人类不良健康后果有关。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。这种污染物很容易穿过胎盘，越来越多的证据表明，发育中的免疫系统比成年人的免疫系统对化学物质的伤害更敏感。然而，很少有研究调查幼年接触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，这些队列的早期生活暴露于砷。我们将利用存档的生物标本来确定产前和产后早期砷暴露情况，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。这将使我们能够实现以下目标：1)确定产前砷暴露与传染病发病率之间的关系；2)确定产前砷暴露与针对人类病原体的体液免疫发育之间的关系；3)探索产前砷与配对脐带婴儿血液样本中外周血白细胞免疫谱变化之间的关系。这项研究的完成有望为儿童发育关键时期环境暴露的免疫调节作用提供新的见解。这一信息解决了我们关于易感人群中环境相关浓度砷暴露的发育毒性的知识中的一个重要空白。这项研究的结果将具有临床相关性，并有助于为能够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.