Environmental Determinants of Autoimmunity among African Americans in Coastal SC

描述(由申请人提供)：南卡罗来纳州和佐治亚州海岛的非洲裔美国古拉族人口是确定自身免疫性疾病的环境因素的独特群体，因为他们的遗传混合度低，环境同质性，抗核抗体(ANA)阳性的高流行率，以及患有系统性红斑狼疮(SLE)的多个受影响家庭。由于本地海鲜是市民的主食，海鲜可能受到的污染物污染备受社会人士关注。这种担忧的基础是双重的。首先，在当地的宽吻海豚和红鼓豚体内发现了某些高度持久的有机污染物，特别是多溴二苯醚(PBDEs)和全氟烷基酸(PFAA)，这两种前哨野生动物都是影响人类健康的前哨野生物种。其次，最近确定了这些生物积累的、无处不在的化合物与人类的多种有害健康影响之间的联系，包括免疫系统功能障碍和自身免疫。作为这项建议的一部分，我们将研究随着时间的推移，SLE患者的一级亲属(FDR)暴露在这些特定环境污染物中的免疫学后果，众所周知，这些患者本身患自身免疫性疾病的风险增加。作为此次调查的一部分，收集的信息将用于支持健全的环境公共卫生行动。这一建议的总体假设是，多溴二苯醚和多溴联苯并呋喃类化合物在遗传高危个体中作为自身免疫的环境触发物起致病作用。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古拉族社区中多溴二苯醚和PFAA的暴露负担是有效的假设。2)检验以下假设，即血清中多溴二苯醚和PFAA的水平与SLE患者的一级亲属中是否存在自身免疫相关，以及这些生物积累化合物的水平在暴露于SLE的个人中随着时间的推移而增加，并且增加的速度将与自身免疫的存在相关。3)开发一种算法来识别PBDE和PFAA暴露的高危社区成员，并检验累积暴露与自身免疫的发展和进展直接相关的假设。4)通过督导委员会和公共论坛开展社区外展和教育。5)评估实现教育和研究目标的参与性过程。 与公共健康相关：拟议的研究涉及海岛非裔美国人社区对在当地主食如鱼中发现的持久性有机污染物的生物积累的关切。这项研究将提供关于多溴二苯醚和PFAA作为自身免疫性疾病发生和发展的潜在环境触发物的作用的重要的、目前尚未获得的信息。最终目标是提高环境暴露对人类健康影响的多学科研究的质量和社区的参与，并制定减少暴露和预防自身免疫性疾病的有效战略。

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.