Project 1: Arsenic and Maternal and Infant Immune Function

动物和体外研究都支持低水平砷暴露与免疫功能受损之间的联系。 其功能反映在抑制先天免疫和增加病原体负荷上。少数流行病学 对这种关联的研究主要是从严重暴露的人群中进行的，而且通常涉及的样本很少 这可能取决于生态暴露措施，可能无法推广到世界其他地区。 在这些重度暴露人群中，砷暴露与风险增加有不同程度的相关性。 呼吸道感染、支气管扩张和寄生虫感染以及免疫标志物的变化 功能包括，例如，细胞因子水平（IL-7、IL-2）和T细胞（CD 4/CD 8）比率。本研究的总体目标是 是评估环境相关的砷水平与母婴免疫的关系 在一项正在进行的妊娠队列研究中，1,000名妇女和婴儿的生殖功能 砷的毒性这项正在进行的纵向研究是在以下母婴对中进行的： 新罕布什尔州的居民从威尔斯井中取水，这是砷的潜在来源 exposure.具体来说，我们将扩大这项正在进行的研究，以测试以下新假设：（1）产前 而早期生活中的砷暴露（通过水，食物）与感染风险增加有关， 1岁;（2）砷暴露与妊娠期感染风险增加有关。 其次，我们将评估产前和产后砷暴露与疫苗反应的关系， 年龄1岁（破伤风和白喉抗体滴度）以及砷是否存在个体差异 代谢（母体尿代谢物谱和砷代谢基因多态性）和其他 因素（例如，吸烟、叶酸摄入量）改变了砷对婴儿或母亲感染的影响。改变 免疫功能，特别是在怀孕和幼儿期，对这两方面都有深远的影响 围产期和随后的健康。据我们所知，在美国研究砷对免疫的影响。 母亲和婴儿人群，具有暴露的个体生物标志物和与可能的 敏感性，以前没有做过。

Both animal and in vitro studies support an association of low level arsenic exposure with impaired immune function as reflected in suppression of innate immunity and increased pathogen load. The few epidemiologic studies of this association are primarily from heavily exposed populations -and often involve small sample sizes or rely on ecologic exposure measures, and may not be generalizable to other regions of the world. Arsenic exposure in these heavily exposed populations has been variously associated with an increased risk of respiratory infection, bronchiectasis, and parasitic infection as well as with changed markers of immune function including, e.g., cytokine levels (IL-7, IL-2) and T-cell (CD4/CD8) ratios. The overall goal of this study is to assess the relationship of environmentally relevant levels of arsenic with maternal and infant immune function among 1,000 women and infants enrolled in an ongoing pregnancy cohort study of reproductive toxicities of arsenic. This ongoing longitudinal study is being conducted among mother-infant pairs who are residents of New Hampshire and obtain household water from wells which are a potential source of arsenic exposure. Specifically, we will expand this ongoing study to test the following new hypotheses: (1) prenatal and early life arsenic exposure (via water, food) is associated with an increased risk of infection during the 1st year of life; (2) arsenic exposure is associated with an increased risk of infection during pregnancy. Secondarily, we will assess the relation of pre- and post-natal arsenic exposure with vaccine response at age one year (antibody titers to tetanus and diphtheria) and whether individual variation in arsenic metabolism (maternal urinary metabolite profiles and polymorphisms in arsenic metabolism genes) and other factors (e.g., smoking, folate intake) modify the effects of arsenic on infant or maternal infection. Altered immune function, particularly in pregnancy and early childhood, can have a profound impact on both perinatal and subsequent health. To the best of our knowledge, studying immune effects of arsenic in a U.S. population of mothers and infants with both individual biomarkers of exposure and measures related to likely susceptibility, has not been done previously.