Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
National Health Council (NHC) Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, China.
Front Immunol. 2023 Jan 25;13:1082950. doi: 10.3389/fimmu.2022.1082950. eCollection 2022.
The pathogenesis of autism spectrum disorder (ASD) is not well understood, especially in terms of immunity and inflammation, and there are currently no early diagnostic or treatment methods. In this study, we obtained six existing Gene Expression Omnibus transcriptome datasets from the blood of ASD patients. We performed functional enrichment analysis, PPI analysis, CIBERSORT algorithm, and Spearman correlation analysis, with a focus on expression profiling in hub genes and immune cells. We validated that monocytes and nonclassical monocytes were upregulated in the ASD group using peripheral blood (30 children with ASD and 30 age and sex-matched typically developing children) using flow cytometry. The receiver operating characteristic curves ( and ) and analysis stratified by ASD severity ( and ) showed that they had predictive value using the "training" and verification groups. Three immune cell types - monocytes, M2 macrophages, and activated dendritic cells - had different degrees of correlation with 15 identified hub genes. In addition, we analyzed the miRNA-mRNA network and agents-gene interactions using miRNA databases (starBase and miRDB) and the DSigDB database. Two miRNAs (miR-342-3p and miR-1321) and 23 agents were linked with ASD. These findings suggest that dysregulation of the immune system may contribute to ASD development, especially dysregulation of monocytes and monocyte-derived cells. ASD-related hub genes may serve as potential predictors for ASD, and the potential ASD-related miRNAs and agents identified here may open up new strategies for the prevention and treatment of ASD.
自闭症谱系障碍 (ASD) 的发病机制尚不清楚，特别是在免疫和炎症方面，目前也没有早期诊断或治疗方法。在本研究中，我们从 ASD 患者的血液中获得了六个现有的基因表达综合组转录组数据集。我们进行了功能富集分析、PPI 分析、CIBERSORT 算法和 Spearman 相关性分析，重点关注了枢纽基因和免疫细胞的表达谱。我们使用流式细胞术（30 名 ASD 儿童和 30 名年龄和性别匹配的典型发育儿童）验证了外周血中单核细胞和非经典单核细胞在 ASD 组中上调。使用“训练”和验证组进行的 ROC 曲线（和）和 ASD 严重程度分层分析（和）表明它们具有预测价值。三种免疫细胞类型 - 单核细胞、M2 巨噬细胞和活化树突状细胞 - 与 15 个鉴定出的枢纽基因具有不同程度的相关性。此外，我们使用 miRNA 数据库（starBase 和 miRDB）和 DSigDB 数据库分析了 miRNA-mRNA 网络和药物 - 基因相互作用。两种 miRNA（miR-342-3p 和 miR-1321）和 23 种药物与 ASD 相关。这些发现表明，免疫系统的失调可能导致 ASD 的发生，特别是单核细胞和单核细胞衍生细胞的失调。ASD 相关的枢纽基因可能作为 ASD 的潜在预测因子，这里确定的潜在 ASD 相关 miRNA 和药物可能为 ASD 的预防和治疗开辟新的策略。
