Mercury (Hg) shown to induce autoimmune disease in rodents is a ubiquitous toxicant throughout Cheyenne River Sioux Tribe (CRST) lands. for ANA ≥ 2+. Although ANA was not significantly associated with Hg the interactions of gender with Hg and proximity to arsenic deposits were statistically significant (< 0.05). FC resulted in a detectable body burden of Hg but THg alone did not correlate with the presence of ANA or sAuAb in this populace. 1 Introduction For more than a century mining from greater than 900 mines in the Black Hills including platinum mines in which Hg was utilized for amalgamation purposes has released contaminants into watersheds draining onto CRST lands [1]. Additionally approximately one ton PQ 401 of airborne Hg is usually emitted per year from coal power plants in Montana Wyoming North Dakota and South Dakota [2] and carried downwind to CRST lands where precipitation and dust wash this mercury out of the air flow into water and soil. Thus Hg is usually virtually ubiquitous throughout the CRST reservation. Studies over the last decade conducted by the tribe United States Environmental Protection Agency (USEPA) and University or college of Colorado [3] have documented high mercury concentrations in mid-flow water samples and sediment [4] invertebrates [5] and fish [5-7]. As PQ 401 a result of the widespread presence of Hg in the environment fish consumption warnings have been posted along the Cheyenne River since 1974 yet no comprehensive health studies have ever been conducted in the CRST populace to assess the health effects of consuming fish from tribal waters. In spite of posted warnings CRST users still consume locally caught fish for complex reasons. Fishing and fish consumption are not only important in Lakota culture but high rates of poverty (~50%) [8 9 and unemployment (88%) [10] around the CRST reservation increase the community’s likelihood of using fish to supplement household subsistence. Therefore the safety PQ 401 of eating mercury-contaminated fish caught on tribal lands was a primary concern for CRST users. To address the CRST’s environmental health concerns a research partnershipororganic mercury exacerbates and accelerates the development of lupus-like disease in susceptible mouse strains [18-21]. Rodent models PQ 401 of mercury-induced autoimmunity [22-24] as well as their regularity with sex differences in autoimmune disease incidence observed in humans suggest it is biologically plausible that Hg and other metals contribute to autoimmune pathogenesis in humans. Yet with the exception of a few epidemiologic studies investigating the role of mercury amalgam fillings in multiple sclerosis [25 26 and studies of ANA and cytokines in mercury-exposed Amazonian Brazil populations [27-30] too few [31 32 have investigated the potential role of chronic environmental metal exposures as risk factors in the development of AD in humans. While associations between metal exposure and immune dysfunction have been exhibited in animals limited data exist in Rabbit polyclonal to ACSS2. humans. Since Hg has long been linked to development of AD-like symptoms in animal models [17] we hypothesized PQ 401 that increased mercury exposure primarily through fish consumption would be associated with higher levels of circulating autoantibodies in the CRST populace. In order to test this hypothesis and respond to community issues we modeled ANA and specific autoantibody concentrations in blood collected from CRST community users using THg fish consumption smoking age gender and proximity to high-concentration arsenic sediment deposits as predictors. 2 Materials and Methods 2.1 Human Subjects The protocol and study design were approved by the Executive Committee of the Cheyenne River Sioux Tribe Tribal Council (Tribal Resolution number: E-302-08-CR and extended under E-343-2009-CR) and by the University or college of New Mexico Health Sciences Center Human Research Protection Office (HRPO number: 08-486). As deidentified serum samples were sent to the Scripps Research Institute PQ 401 Department of Molecular and Experimental Medicine the Scripps Research Institute’s Institutional Review Table provided approval for an analysis of serum ANA and specific autoantibodies. Participants were recruited by using community-based communication tools and procedures previously developed by this team and applied in theEnvironmental Justice on Cheyenne Riverstudy. Outreach.