Immunotoxicity in Humans with Lifetime Exposure to Ocean Pullutants

描述(由申请人提供) 海鲜是人类接触环境污染物的主要来源，如甲基汞和包括多氯联苯在内的亲脂污染物。此外，全氟化合物(PFC)在海洋食物链中具有生物放大作用，在营养水平较高的海洋哺乳动物中浓度最高。研究人员最近发现，全氟化碳可能会对人类免疫系统的发育产生不利影响。因此，在法罗群岛儿童中，暴露于PFC的增加与对儿童常规免疫接种的体液免疫反应降低有关。研究人员现在建议通过利用现有和独特的法罗人和格陵兰人出生的队列来扩大这一观察结果，这些人的海鲜摄入量和海洋食物链中高海洋哺乳动物的传统消费水平很高。由于可获得广泛的基线数据，对出生队列(来自每个人口的250名受试者)的免疫功能进行后续检查是可行的，并将涵盖从早教年龄到年轻成人在不同生命阶段，包括宫内暴露的结果。作为主要结果，他们将评估儿童免疫后血清中特定抗体的浓度。研究人员还将确定28岁成年人对加强剂量(白喉和破伤风)和接种新抗原(甲型和乙型肝炎)的免疫反应。他们将记录过敏性疾病的发生情况，并测量血清总IgE和特异性IgE的浓度，作为与产前和出生后暴露相关的可能的免疫毒性结果。将使用先进的统计模型来确定全氟化碳和其他海洋污染物在不同发展阶段的相对贡献，并计算用于风险评估的基准剂量水平。这一新证据将对了解终生暴露于全氟化碳和来自海洋食品的其他免疫毒性污染物的人的免疫毒性以及这些海洋污染物的风险评估具有重要意义。 公共卫生相关性：研究人员将检查法罗群岛和格陵兰的两个出生队列的免疫功能，这些出生队列暴露于来自海鲜摄入的潜在免疫毒性海洋污染物的风险增加。作为免疫功能的敏感指标，它们将评估儿童免疫的抗体反应、成人接种疫苗的效率以及成年前过敏的发生情况，并将它们与产前或以后生命阶段发生的接触联系起来。这一结果将为保护海洋免受 用于防止污染物和对海产品消费者的不利影响。

DESCRIPTION (provided by applicant) Seafood is a main source of human exposure to environmental pollutants, such as methyl mercury and lipophilic contaminants, including polychlorinated biphenyls (PCBs). In addition perfluorinated compounds (PFCs) biomagnify in ocean food chains, with the highest concentrations in marine mammals at high trophic levels. The investigators recently discovered that PFCs may adversely impact on human immune system development. Thus, in Faroese children, elevated PFC exposures were associated with reduced humoral immune response to routine childhood immunizations. The investigators now propose to extend this observation by utilizing existing and unique birth cohorts of Faroese and Greenlanders with high levels of seafood intake and traditional consumption of marine mammals high in ocean food chains. Due to the availability of extensive baseline data, follow-up examination of immune functions in the birth cohorts (250 subjects from each population) is feasible and will encompass outcomes at early school age through to young adult age in regard to exposures at different life stages, including intrauterine. As the main outcome, they will assess concentrations of specific antibodies in serum in response to childhood immunizations. The investigators will also determine the immune response in adults aged 28 to a booster dose (diphtheria and tetanus) and to vaccination with new antigens (hepatitis A and B). They will record the occurrence of allergic diseases and measure serum concentrations of total and specific IgE as possible immunotoxicity outcomes associated with prenatal and postnatal exposures. Advanced statistical models will be used to determine the relative contributions by PFCs and other ocean pollutants at different developmental stages and calculate benchmark dose levels for use in risk assessment. This new evidence will be of substantial importance for the understanding of immunotoxicity in humans with lifetime exposure to PFCs and other immunotoxic pollutants from marine food and for the risk assessment of these ocean pollutants. Public Health Relevance: The investigators will examine immune functions in two birth cohorts in the Faroe Islands and Greenland with elevated exposures to potentially immunotoxic ocean pollutants from seafood intake. As sensitive measures of immune functions, they will assess antibody responses to childhood immunizations, efficiency of vaccinations at adult age, and occurrence of allergy up to adult age, and link them to exposures incurred prenatally or during later life stages. The results will provide new insight needed for the protection of oceans against pollutants and for prevention of adverse effects in seafood-consumers.