Project 2: Development of biomarkers of autoimmunity in 3 tribal communities exposed to mixed metal contaminants

研究项目2 废弃矿山废物的高度集中和部落社区的农村性质往往带来 社区成员直接和频繁地接触未经补救的低水平金属混合物， 废弃的矿场，导致通过吸入、饮用水和 直接或间接受到废物污染的食物来源。的目标 研究项目2（RP 2）是评估金属暴露的关系（通过生物监测确定， 血液和尿液样本）与来自部落社区的个体的免疫结果， 靠近遗留的矿山废物。这一目标直接回应了部落社区的关切， 长期暴露于金属和类金属混合物会影响免疫反应， 疾病我们的总体假设是，由于环境因素， 接触到部落社区内的混合金属污染物，这种接触导致免疫 失调和自身免疫反应。我们将1）确定是否暴露于金属或金属 混合物（通过生物监测测量）增加抗核抗体（ANA）和/或 淋巴细胞凋亡从我们的三个受影响的部落社区的个人。2)确定是否 暴露于金属或金属混合物与细胞因子谱或T和B的可预测变化相关 细胞表型在个人从我们的三个部落人口和3）确定的影响，金属混合物 与我们三个参与的部落社区有关的自身免疫性疾病的加重或诱导， 在体内动物模型中通过饮用水暴露引起免疫失调。一根本性的问题 这些研究所涉及的是环境金属的某些组合是否具有独立的， 相加，甚至协同毒性作用。部落社区不成比例地受到各种 重金属和类金属，但没有以人口为基础的研究调查混合金属的影响 暴露对免疫反应的影响，特别是在不同的部落社区， 环境金属我们有独特的机会在三个不同的领域使用相同的研究方法。 美洲原住民部落人口，以明确确定共同点和不同的接触， 暴露结果。本研究的一个主要目标和创新是开发一个通用数据库， 来自三个部落社区（计划扩展到其他社区）的关于接触和结果的数据 免疫学参数从未被编辑过这些数据对于建立 这些社区的暴露和健康结果的共同点和重叠， 健康方面存在差距。

Summary-Research Project 2 The high concentration of abandoned mine waste and rural nature of Tribal communities often brings community members into direct and frequent contact with low-level metal mixtures from un-remediated and abandoned mine sites, resulting in potentially toxic exposures occurring via inhalation, drinking water, and ingestion of food sources that are either directly or indirectly contaminated by wastes. The objective of research project 2 (RP2) is to assess the relationship of metal exposures (determined through biomonitoring of blood and urine samples) with immunologic outcomes in individuals from Tribal communities who live in proximity to legacy mine waste. This objective responds directly to concerns of the Tribal communities that chronic exposure to metal and metalloid mixtures affects immune responses and contributes to development of disease. Our overarching hypothesis is that there is an increased body burden of metals due to environmental exposure to mixed metal contaminants within the Tribal communities, and that this exposure results in immune dysregulation and autoimmune responses. We will 1) Determine whether exposure to metals or metal mixtures (measured through biomonitoring) increases the prevalence of anti-nuclear antibodies (ANA) and/or lymphocyte apoptosis in individuals from our three affected Tribal communities. 2) Determine whether exposure to metals or metals mixtures are associated with predictable changes in cytokine profiles or T and B cell phenotypes in individuals from our three Tribal populations and 3) Determine the effect of metal mixtures relevant to our three participating Tribal communities on exacerbation or induction of autoimmune disease and immune dysregulation via a drinking water exposure in in vivo animal models. A fundamental question addressed by these studies is whether certain combinations of environmental metal have independent, additive, or even synergistic toxic effects. Tribal communities are disproportionately exposed to a variety of heavy metals and metalloids, yet there are no population-based studies investigating the effect of mixed metals exposure on immune responses, especially across different Tribal communities with exposures to environmental metals. We have the unique opportunity to use the same research approaches on three different Native American Tribal populations to clearly identify commonalities and differences in exposures and exposure outcomes. A major goal and innovation of this study is the development of a common database with data from three Tribal communities (with planned expansion to other communities) on exposure and resulting immunologic parameters that have never been compiled. This data will be crucial to establishing commonalities and overlaps in exposures and health outcomes in these communities for which such significant health disparities exist.