Preventive Medicine & Pediatrics Departments, Loma Linda University, Loma Linda, CA, USA.
Department of Psychiatry and Behavioral Sciences & Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, CA, USA.
Dev Psychopathol. 2022 Aug;34(3):875-881. doi: 10.1017/S095457942000187X. Epub 2021 Jan 28.
This study evaluated whether children with higher adverse childhood experiences (ACE) scores had alterations in immune cell gene expression profiles. RNA sequencing was conducted on dried blood spot samples from 37 generally healthy English-speaking children (age 5-11) who were recruited from well-child visits at a university-affiliated pediatric practice. The Whole Child Assessment was used to assess ACE exposure. Primary analyses examined an a priori-specified composite of 19 pro-inflammatory gene transcripts. Secondary analyses examined a 34-gene composite assessing Type I interferon response, and used Transcript Origin Analyses to identify cellular mechanisms. After controlling for age, body mass index percentile, sex, race/ethnicity, current insurance status, and household smoking exposure, pro-inflammatory gene expression was elevated by 0.094 log2 RNA expression units with each Child-ACE total score point ( = .019). Type I interferon gene expression was similarly upregulated (0.103; = .008). Transcript origin analyses implicated CD8+ T cell as the primary sources of gene transcripts upregulated, and nonclassical (CD16+) monocytes as sources of downregulated transcripts. These preliminary analyses suggest that parent-reported ACE exposures are associated with increased expression of both inflammatory and interferon gene transcripts in children's circulating blood cells.
本研究评估了 ACE 得分较高的儿童是否存在免疫细胞基因表达谱的改变。从参加大学附属儿科诊所定期儿童健康检查的 37 名英语为母语的一般健康儿童(年龄 5-11 岁)的干血斑样本中进行了 RNA 测序。采用全儿童评估(Whole Child Assessment)来评估 ACE 暴露情况。主要分析检验了预先指定的 19 个促炎基因转录本的综合指标。次要分析检验了评估 I 型干扰素反应的 34 个基因综合指标,并使用转录本起源分析来识别细胞机制。在控制年龄、体重指数百分位、性别、种族/民族、当前保险状况和家庭吸烟暴露后,每个儿童 ACE 总分点使促炎基因表达升高 0.094log2 RNA 表达单位(=0.019)。I 型干扰素基因表达也类似地被上调(0.103;=0.008)。转录本起源分析表明,CD8+T 细胞是上调基因转录本的主要来源,非经典(CD16+)单核细胞是下调转录本的来源。这些初步分析表明,父母报告的 ACE 暴露与儿童循环血细胞中炎症和干扰素基因转录本的表达增加有关。