Environmental Determinants of Autoimmunity among African Americans in Coastal SC

描述（由申请人提供）：南卡罗来纳和乔治亚州海岛上的非裔美国人格勒人是一个独特的社区，因为他们的遗传混合度低、环境同质性强、抗核抗体（ANA）阳性的高发率，以及患有系统性红斑狼疮（SLE）的多种疾病的家庭，他们可以定义自身免疫性疾病的环境因素。由于本地海产品是人们的主要食物，因此海产品可能受到的污染物污染是社会高度关注的问题。这种担忧的基础是双重的。首先，某些高度持久性有机污染物（POPs）含量很高，特别是多溴联苯醚（PBDEs）和全氟烷基酸（PFAAs），在当地的宽吻海豚和红鼓中被发现，这两种野生动物都是人类健康影响的替代品。其次，最近建立了这些生物积累、无处不在的化合物与人类多种有害健康影响（包括免疫系统功能障碍和自身免疫）之间的联系。作为该提案的一部分，我们将研究SLE患者一级亲属（fdr）长期暴露于这些特定环境污染物相关的免疫学后果，已知这些患者自身表现出更高的自身免疫性疾病风险。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。该建议的总体假设是，多溴二苯醚和PFAAs在遗传风险个体中作为自身免疫的环境触发因素发挥致病作用。我们将通过实现以下具体目标来检验这一假设：1)为了验证居住，职业和食物频率问卷是有效评估的负担接触多溴二苯醚和PFAAs格勒在非洲裔美国人社区生活在南卡罗来纳的海岛地区。2)来测试假设血清水平的多溴二苯醚和PFAAs将与自身免疫的存在之间的系统性红斑狼疮患者的一级亲属,这些化合物具有提高水平随着时间的推移,个人接触和内部的速度增加与自身免疫有关3)建立识别多溴二苯醚和PFAA暴露高风险社区成员的算法，并验证累积暴露与自身免疫的发生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工作。5)评估参与性过程在达到教育和研究目标方面的作用。

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.