Amine Ines, Anguita-Ruiz Augusto, Guillien Alicia, Basagaña Xavier, Bustamante Mariona, Borràs Eva, Cirach Marta, Dedele Audrius, Dobaño Carlota, Garcia-Aymerich Judith, Granum Berit, Grazuleviciene Regina, González Juan Ramón, Julvez Jordi, Keun Hector, López-Vicente Mónica, McEachan Rosemary, Moncunill Gemma, Nieuwenhuijsen Mark, Sabidó Eduard, Slama Rémy, Tenenhaus Arthur, Vafeiadi Marina, Wright John, Yang Tiffany, Yuan Wen Lun, Vrijheid Martine, Siroux Valérie, Maitre Léa
Université Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Team of Environmental Epidemiology Applied to the Development and Respiratory Health, 38700 La Tronche, France.
ISGLobal, Barcelona, Spain; CIBEROBN, (Physiopathology of Obesity and Nutrition CB12/03/30038), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain.
Environ Int. 2025 Aug;202:109668. doi: 10.1016/j.envint.2025.109668. Epub 2025 Jul 5.
Early-life environmental exposures are suspected to modify important immune processes related to child health. Yet, no study has investigated immunotoxicity in relation to the exposome and multiple health domains simultaneously.
Among 845 children (median age 8) from six European birth cohorts included in the Human Early-Life Exposome (HELIX) project, we identified immune signatures of a health score covering cardiometabolic, respiratory/allergic and neurodevelopmental health in children. Those signatures were identified from blood samples in three biological layers (white blood cell (WBC) composition, plasma proteins concentrations, DNA methylation of WBCs) using an advanced factorial analysis supervised on the child health score. Second, we estimated the association between the identified signatures and 91 pre- and postnatal environmental exposures.
Three key immune signatures were associated with a better health score in children: a first protein signature characterizing a low inflammatory profile (R = 17 %), a second protein signature characterizing a low inflammatory profile with balanced antiviral Th response (R = 2 %), and a WBC signature characterizing an immuno-regulatory and naïve profile (R = 2 %). In childhood, less exposure to indoor air pollutants, proximity to blue spaces and public transport, healthy dietary habits and higher social capital were associated with the three immune signatures related to a better health score (regression p-values < 0.05). One signature was identified from DNA methylation, but was not significantly associated with the health score nor with the exposome.
These findings highlight the influence of early-life environmental exposures on key inflammatory processes associated with the cardiometabolic, respiratory and neurodevelopmental health of children.
早年的环境暴露被怀疑会改变与儿童健康相关的重要免疫过程。然而，尚无研究同时调查与暴露组和多个健康领域相关的免疫毒性。
在纳入人类早期生活暴露组（HELIX）项目的六个欧洲出生队列的845名儿童（中位年龄8岁）中，我们确定了涵盖儿童心脏代谢、呼吸/过敏和神经发育健康的健康评分的免疫特征。这些特征是从三个生物层面（白细胞（WBC）组成、血浆蛋白浓度、WBC的DNA甲基化）的血样中，使用基于儿童健康评分的高级因子分析确定的。其次，我们估计了所确定的特征与91种产前和产后环境暴露之间的关联。
三个关键免疫特征与儿童更好的健康评分相关：第一个蛋白特征表征低炎症状态（R = 17%），第二个蛋白特征表征低炎症状态且抗病毒Th反应平衡（R = 2%），以及一个WBC特征表征免疫调节和幼稚状态（R = 2%）。在儿童期，较少接触室内空气污染物、靠近蓝色空间和公共交通、健康的饮食习惯以及较高的社会资本与与更好健康评分相关的三个免疫特征相关（回归p值<0.05）。从DNA甲基化中确定了一个特征，但与健康评分和暴露组均无显著关联。
这些发现突出了早年环境暴露对与儿童心脏代谢、呼吸和神经发育健康相关的关键炎症过程的影响。
