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

EPA Grant Number: R836157C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R836157
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Center for Native American Environmental Health Equity Research
Center Director: Lewis, Johnnye Lynn
Title: Development of biomarkers of autoimmunity in 3 tribal communities exposed to mixed metal contaminants
Investigators: MacKenzie, Debra Ann , Doyle, John , Erdei, Esther , Keil, Deborah , Murray-Krezan, Cristina , Rubin, Robert L.
Institution: University of New Mexico Health Sciences Center , Montana State University - Bozeman
EPA Project Officer: Breville, Maggie
Project Period: July 1, 2015 through June 30, 2020
RFA: NIH/EPA Centers of Excellence on Environmental Health Disparities Research (2015) RFA Text |  Recipients Lists
Research Category: Health

Objective:

The objective of this project 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. 

Specific Aim 1: Determine whether exposure to metals or metal mixtures increases the prevalence of anti-nuclear antibodies and/or lymphocyte apoptosis in individuals from three affected Tribal communities.

Specific Aim 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 three Tribal populations.

Specific Aim 3: Determine the effect of metal mixtures relevant to three participating Tribal communities on exacerbation or induction of autoimmune disease and immune dysregulation via a drinking water exposure in in vivo animal models.

Approach:

The 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. Investigators 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 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 three Tribal populations and 3) Determine the effect of metal mixtures relevant to 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. These investigators 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.

Rationale:

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. 


Main Center Abstract and Reports:

R836157    Center for Native American Environmental Health Equity Research

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836157C001 Metals and metal mixtures in DNA damage and repair
R836157C002 Development of biomarkers of autoimmunity in 3 tribal communities exposed to mixed metal contaminants