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

项目 2：在暴露于混合金属污染物的 3 个部落社区中开发自身免疫生物标志物

• 批准号: 9118267
• 负责人: Debra MacKenzie
• 金额: $ 15.22万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9118267
• 关键词: Address; Affect; Animal Model; Antibodies; Apoptosis; Autoimmune Diseases; Autoimmune Process; Autoimmune Responses; Autoimmunity; B-Lymphocytes; Biological; Biological Markers; Biological Monitoring; Blood; Body Burden; Breathing; Cells; Chronic; Communities; Data; Databases; Development; Disease; Environmental Exposure; Environmental Health; Environmental Pollution; Experimental Models; Exposure to; Food; Goals; Health; Heavy Metals; Human; Immune; Immune response; Immunologics; Individual; Ingestion; Interleukin-17; Lead; Life; Lymphocyte; Measures; Mediating; Metal exposure; Metals; Mining; Molecular; Native Americans; Nature; Nuclear; Outcome; Phenotype; Population; Prevalence; Production; Research; Research Project Grants; Research Project Summaries; Risk Reduction; Rural; Sampling; Serum; Site; Source; T-Lymphocyte; Therapeutic; Toxic effect; Toxicant exposure; Urine; apoptosis in lymphocytes; biomarker development; cytokine; drinking water; health disparity; health equity; immune function; in vivo; innovation; member; mouse model; population based; response; tribal community; wasting

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.

摘要研究项目2 废弃的矿山废物和部落社区的农村性质的高度集中经常带来 社区成员与未经修复和的低级金属混合物直接接触 废弃的矿场，导致通过吸入，饮用水和 摄入直接或间接污染废物的食物来源。目的 研究项目2（RP2）是为了评估金属暴​​露的关系（通过生物监测确定 血液和尿液样本）居住在部落社区的个体中的免疫结果 靠近传统地雷浪费。这个目标直接回应了部落社区的担忧 长期暴露于金属和金属混合物会影响免疫反应，并有助于发展 疾病。我们的总体假设是由于环境而增加金属的体重 暴露于部落社区内的混合金属污染物，这种暴露会导致免疫 失调和自身免疫反应。我们将1）确定暴露于金属还是金属 混合物（通过生物监测测量）增加了抗核抗体（ANA）和/或 来自我们三个受影响部落社区的个体的淋巴细胞凋亡。 2）确定是否 接触金属或金属混合物与细胞因子谱或T和B的可预测变化有关 来自我们三个部落人群的个体中的细胞表型和3）确定金属混合物的影响 与我们三个参与的部落社区有关，以加剧或诱导自身免疫性疾病和 通过体内动物模型中饮用水暴露的免疫失调。一个基本问题 这些研究解决的是环境金属的某些组合是否具有独立 添加剂，甚至协同的有毒作用。部落社区不成比例地接触到各种各样的 重金属和金属素，但没有基于人群的研究来研究混合金属的影响 免疫反应的接触，尤其是在不同部落社区的情况下 环境金属。我们有独特的机会在三种不同的情况下使用相同的研究方法 美国原住民部落人口清楚地识别暴露和差异 暴露结果。这项研究的主要目标和创新是开发一个常见数据库 来自三个部落社区（计划向其他社区扩展）的数据， 从未收集过的免疫学参数。这些数据对于建立至关重要 这些社区的暴露和健康成果的共同点和重叠，这些社区如此重要 存在健康差异。