Environmental Determinants of Autoimmunity among African Americans in Coastal SC

描述（由申请人提供）：南卡罗来纳州和格鲁吉亚海岛的非裔美国人Gullah人群是一个独特的社区，由于其遗传混合性低、环境同质性和抗核抗体（ANA）阳性的高患病率以及系统性红斑狼疮（SLE）多发性受累的家族，其定义了自身免疫性疾病的环境因素。由于本港市民的主要食物是海产，海产可能受到污染，因此备受市民关注。这一关切有两方面的依据。首先，在当地的海豚和红鼓中发现了高水平的某些高持久性有机污染物，特别是多溴联苯醚和全氟烷基酸，这两种野生动物物种都是人类健康影响的替代品。其次，最近在这些生物积累性的、普遍存在的化合物与人类多种有害健康影响之间建立了联系，包括免疫系统功能障碍和自身免疫。作为这项提案的一部分，我们将研究与接触这些特定的环境污染物随着时间的推移在一级亲属（FDR）的SLE患者，谁是已知的表现出发展自身免疫性疾病的风险增加的免疫后果。作为调查的一部分收集的信息将用于支持健全的环境公共卫生行动。该提案的总体假设是，多溴二苯醚和全氟辛酸作为环境因素触发了遗传风险个体的自身免疫，发挥了致病作用。我们将通过实现以下具体目标来检验这一假设：1）检验居住、职业和食物频率问卷对于评估居住在南卡罗来纳州海岛地区的非裔美国人Gullah社区中多溴二苯醚和全氟辛酸接触负担的有效性这一假设。2)检验以下假设：多溴联苯醚和全氟辛酸血清水平与系统性红斑狼疮患者一级亲属中自身免疫的存在相关，以及这些生物累积化合物的水平在接触者体内随时间推移而增加，且增加率与自身免疫的存在相关。3)制定一种算法，以确定多溴二苯醚和全氟辛酸接触的高风险社区成员，并检验累积接触与自身免疫的发展和进展直接相关的假设。4)透过督导委员会及公众论坛进行社区外展及教育。5)评估实现教育和研究目标的参与过程。 公共卫生相关性：拟议的研究针对的是海岛非洲裔美国人社区对在当地斯台普斯（如鱼类）中发现的持久性有机污染物的生物累积性的关切。这项研究将提供关于多溴二苯醚和全氟辛烷磺酸作为自身免疫性疾病发展和进展的潜在环境触发因素的作用的重要的、目前尚不可用的信息。最终目标是提高关于环境暴露对人类健康影响的多学科研究的质量和社区参与，并制定减少暴露和预防自身免疫疾病的有效战略。

DESCRIPTION (provided by applicant): The African American Gullah population of the Sea Islands of South Carolina and Georgia are a unique community for defining environmental factors for autoimmune diseases due to their low genetic admixture, environmental homogeneity, and a high prevalence of anti-nuclear antibody (ANA) positivity and families with multiple affecteds with systemic lupus erythematosus (SLE). With local seafood consumption being a dietary staple, potential pollutant contamination of the seafood is of high concern to the community. The basis for this concern is twofold. First, high levels of certain highly persistent organic pollutants (POPs), specifically polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl acids (PFAAs), are found in local bottlenose dolphins and red drum, both sentinel wildlife species that serve as surrogates of human health effects. Second, links were recently established between these bioaccumulating, ubiquitous compounds and multiple deleterious health effects in humans, including immune system dysfunction and autoimmunity. As part of this proposal, we will study the immunological consequences associated with exposure to these specific environmental contaminants over time in first-degree relatives (FDRs) of patients with SLE, who are known to exhibit an increased risk of developing autoimmune disease themselves. The information gathered as part of this investigation will be used to support sound environmental public health action. The overall hypothesis of this proposal is that PBDEs and PFAAs play a pathogenic role as environmental triggers of autoimmunity in genetically at-risk individuals. We will test this hypothesis by accomplishing the following Specific Aims: 1) To test the hypothesis that residential, occupational and food frequency questionnaires are valid for assessing the burden of exposure to PBDEs and PFAAs among the African American Gullah community living in the Sea Island areas of South Carolina. 2) To test the hypothesis that serum levels of PBDEs and PFAAs will correlate with the presence of autoimmunity among first-degree relatives of patients with SLE and that levels of these bioaccumulating compounds increase over time within individuals exposed and that the rate of increase will correlate with the presence of autoimmunity. 3) To develop an algorithm to identify community members at high-risk for PBDE and PFAA exposure and test the hypothesis that cumulative exposure directly correlates with development and progression of autoimmunity. 4) To perform community outreach and education through a Steering Committee and public forums. 5) To evaluate the participatory process in reaching the educational and research objectives. PUBLIC HEALTH RELEVANCE: The proposed studies address concerns of the Sea Island African American community regarding bioaccumulating persistent organic pollutants found in local dietary staples such as fish. This study will provide important, not currently available information regarding the role of PBDEs and PFAAs as potential environmental triggers for the development and progression of autoimmune disease. The ultimate goal is to improve the quality of and community participation in multidisciplinary research on the human health effects of environmental exposures and develop effective strategies for exposure reduction and autoimmune disease prevention.