Biochemistry Department, Science College, King Saud University, Riyadh, Saudi Arabia.
Autism Research and Treatment Center, Riyadh, Saudi Arabia.
Metab Brain Dis. 2018 Aug;33(4):1141-1153. doi: 10.1007/s11011-018-0206-6. Epub 2018 Mar 22.
Autism spectrum disorder (ASD) is a multifactorial disorder caused by an interaction between environmental risk factors and a genetic background. It is characterized by impairment in communication, social interaction, repetitive behavior, and sensory processing. The etiology of ASD is still not fully understood, and the role of neuroinflammation in autism behaviors needs to be further investigated. The aim of the present study was to test the possible association between prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin PGE2 EP2 receptors and nuclear kappa B (NF-κB) and the severity of cognitive disorders, social impairment, and sensory dysfunction. PGE2, COX-2, mPGES-1, PGE2-EP2 receptors and NF-κB as biochemical parameters related to neuroinflammation were determined in the plasma of 47 Saudi male patients with ASD, categorized as mild to moderate and severe as indicated by the Childhood Autism Rating Scale (CARS) or the Social Responsiveness Scale (SRS) or the Short Sensory Profile (SSP) and compared to 46 neurotypical controls. The data indicated that ASD patients have remarkably higher levels of the measured parameters compared to neurotypical controls, except for EP2 receptors that showed an opposite trend. While the measured parameter did not correlate with the severity of social and cognitive dysfunction, PGE2, COX-2, and mPGES-1 were remarkably associated with the dysfunction in sensory processing. NF-κB was significantly increased in relation to age. Based on the discussed data, the positive correlation between PGE2, COX-2, and mPGES-1 confirm the role of PGE2 pathway and neuroinflammation in the etiology of ASD, and the possibility of using PGE2, COX-2 and mPGES-1 as biomarkers of autism severity. NF-κB as inflammatory inducer showed an elevated level in plasma of ASD individuals. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of biochemical correlates to ASD.
自闭症谱系障碍（ASD）是一种由环境风险因素和遗传背景相互作用引起的多因素疾病。其特征为沟通、社交互动、重复性行为和感官处理受损。ASD 的病因仍不完全清楚，神经炎症在自闭症行为中的作用需要进一步研究。本研究旨在测试前列腺素 E2（PGE2）、环氧化酶-2（COX-2）、微粒体前列腺素 E 合酶-1（mPGES-1）、前列腺素 PGE2 EP2 受体和核因子-κB（NF-κB）与认知障碍、社交障碍和感官功能障碍严重程度之间的可能关联。在 47 名沙特男性 ASD 患者的血浆中测定了与神经炎症相关的生化参数 PGE2、COX-2、mPGES-1、PGE2-EP2 受体和 NF-κB，根据儿童自闭症评定量表（CARS）或社交反应量表（SRS）或短感官评估（SSP）将患者分为轻度至中度和重度，并与 46 名神经典型对照进行比较。数据表明，与神经典型对照组相比，ASD 患者的这些测量参数明显更高，除了 EP2 受体呈现相反的趋势。虽然这些测量参数与社交和认知功能障碍的严重程度无关，但 PGE2、COX-2 和 mPGES-1 与感官处理障碍明显相关。NF-κB 与年龄呈显著正相关。根据讨论的数据，PGE2、COX-2 和 mPGES-1 的正相关证实了 PGE2 途径和神经炎症在 ASD 发病机制中的作用，并且有可能将 PGE2、COX-2 和 mPGES-1 用作自闭症严重程度的生物标志物。作为炎症诱导剂的 NF-κB 在 ASD 个体的血浆中显示出升高的水平。接受者操作特征分析和预测图证明，这些测量参数可用作 ASD 的生化相关性的预测生物标志物。
