College of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, 410128, China.
Sci Rep. 2023 Aug 28;13(1):14040. doi: 10.1038/s41598-023-40617-4.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets.
自闭症谱系障碍(ASD)是一种神经发育障碍,通常在儿童时期表现出来,被认为是遗传、环境和免疫因素复杂相互作用的结果。目前大多数 ASD 的诊断方法依赖于主观的行为观察和量表评估,这使得早期检测变得困难。在这项研究中,我们通过生物信息学方法证实,溶酶体相关膜蛋白 1(LAMP1)作为免疫细胞激活和细胞毒性脱粒的功能标志物,在 ASD 血液、大脑皮层和各种遗传动物模型或细胞中上调。我们通过将 LAMP1 的表达与临床 ASD 评分量表相关联,来研究其预后价值,在 ASD 中的受试者工作特征(ROC)曲线分析也表明,它在区分 ASD 与对照组方面具有良好的诊断能力。根据基因集富集分析(GSEA)的结果,LAMP1 与在自然杀伤和 T 细胞免疫功能中富集的基因相关。综合所有证据,我们发现 ASD 儿童血液中 LAMP1 mRNA 和蛋白的异常升高,可能通过参与免疫细胞活性调节,影响 ASD 的发展。本报告强调了一种用于 ASD 早期检测的新型标志物,以及潜在的治疗靶点。