Metal mixture exposures and multiplexed autoantibody screening in Navajo communities exposed to uranium mine wastes

Background: Environmental exposures to metals in uranium mining wastes and drinking water were documented in more than half of the 1304 Navajo community members of the Dine ' Network for Environmental Health (DiNEH) Project, the first comprehensive assessment of exposures to these metals and community health on the Navajo Nation.Objective: Evaluate environmental exposures among participants who provided blood and urine samples using multiplexed autoantibody positivity as an early effect biomarker.Methods: Survey and geospatial location data, well water quality, and metals biomonitoring were used to assess exposures to mixed-metal wastes from 100 abandoned uranium waste sites.Results: We observed that the prevalence of multiplexed autoantibody positivity in 239 participants was more than double that reported for the U.S. population (27.2% v. 13.8%) even though the national prevalence was generated using a different assay, the HEp-2 cell-based antinuclear antibody test. Increased risk of multiplexed autoantibody screening positivity (OR = 3.07,95%CI 1.15-8.22) was found among DiNEH study people who lived close to uranium mine and milling wastes and consumed metals in drinking water. Associations for females were even stronger when they lived closed to contaminated uranium mining and milling sites. Anti-U1-RNP antibodies were associated with water consumption of nickel.Conclusion: Proximity to waste sites and consumption of metals in water even below current drinking water standards were associated with perturbations of immune tolerance. These findings are consistent with previous studies of autoimmunity in the local population and demonstrate that multiplexed autoantibody screening method has a potential as sentinel indicator of exposures to environmental metals.Impact statement: This is the first, community-engaged environmental health study in exposed Navajo communities that applied clinical multiplexed testing in risk assessment of environmental metals associated with abandoned, unremediated uranium mining and milling waste sites. Routine clinical autoimmunity measures could be used as early effect biomarkers of environmental metal exposures.