Patterns of Autoimmune Biomarkers among Metal/Metalloid and Organochemical-Exposed Native American/Alaska Native Tribal members

Tribal communities have been struggling for decades with many gene-associated, environmentally-induced chronic diseases, such as type II diabetes, cardiovascular diseases, stroke, and several types of cancers, all of which have been associated with preexisting immune system alterations or hyperreactivities. Our team have shown that exposure to metals/metalloids is strongly associated with immune system dysfunction and autoimmune biomarkers such as antinuclear antibodies (ANA) and organ/tissue-specific autoantibodies and these biomarkers can be applied successfully as early effect measures in exposed communities. Evolving scientific gap about other emerging chemical exposures and their adverse health effects research however, points toward the need to extend the only metal/metalloid focused assessments to include organochemical analyses such as PFAS, ‘forever chemicals”. Furthermore, our Team also developed novel biostatistical modeling approaches to characterize both metal/metalloids and PFAS exposure patterns as mixtures using community-based samples. This study will establish a Tribal community-level environmental exposure and autoimmunity data repository using previously collected and stored biobanked samples. These in total will represent more than 15 Tribes living in 5 states. Samples will be provided by the NIH/NHLBI- supported Strong Heart Study/Strong Heart Family Study (N=700), the CDC’s Alaska Area Specimen Bank (N=186) and the PI’s NARCHVII study among Lakota fisher folks (N=225). This will create the largest Tribal Biospecimen Repository (N=1,111) that is going to address the following goals: Specific Aim 1. To quantify levels of 43 (both short- and long-chain) PFAS from serum samples and 24 different toxic metals and metalloids from urine samples previously collected from adult Tribal residents. Specific Aim 2a. Determine serum antinuclear antibody staining (> 2+) intensity using the ‘gold standard’ antinuclear autoantibody (ANA) and the presence of serum anti-thyroid specific autoantibodies (anti-TPO and anti-thyroglobulin). Specific Aim 2b. To examine the development of these autoimmunity biomarkers in the SHS/SHFS samples, collected from the same Tribal participants 10 years part. This sub-aim targets the critical question of environmentally induced autoantibody production. Specific Aim 3. To evaluate the relationships of PFAS, modelled individually and as a mixture with metals and model autoimmune marker outcomes. Then these will be compared and contrasted with the NHANES nationwide antinuclear antibody (ANA) and exposure database information (1990-2018).