Department of Maternal, Child & Adolescence Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Department of Maternal, Child & Adolescence Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Neuroscience. 2021 Jun 15;465:95-104. doi: 10.1016/j.neuroscience.2021.04.006. Epub 2021 Apr 22.
Increasing evidence suggests that immunological disturbances and abnormalities in axonal myelination are involved in the pathophysiology of autism spectrum disorder (ASD). The present study aimed to determine the role of cytokines in myelin damage in Chinese children with ASD and the role of cytokine dysregulation, myelin damage, and cytokine polymorphisms in ASD in Chinese children. The present case-control study included 98 ASD subjects and 252 typically developing (TD) controls; the levels of serum cytokines and myelin basic protein (MBP) were determined using enzyme-linked immunosorbent assay. Cytokine polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Autistic clinical manifestations were assessed by the Childhood Autism Rating Scale (CARS). The results showed that serum levels of interleukin (IL)-1β, IL-2R, IL-6, IL-8, and MBP were higher in children with ASD compared with those in TD children. In individuals with ASD, serum MBP level was significantly positively associated with the CARS total score, and serum levels of IL-1β, IL-2R, IL-6, and MBP demonstrated positive correlations. The data identified IL-6MBP as a factor that influenced the risk of ASD, and IL-2RMBP was identified as a factor that influenced symptom severity, which influenced auxiliary diagnosis of ASD. The presence of the interleukin-6-572CC genotype was associated with significantly higher serum levels of IL-6 and MBP but did not influence the risk and symptom severity of ASD. Therefore, the results suggested inflammatory responses and myelin damage in Chinese children with ASD. Cytokine dysregulation influenced myelin damage in ASD; moreover, the interactions of the cytokines and myelin damage influenced the risk and symptom severity of ASD. The IL-6-572C/G genotypes may be associated with myelin damage in ASD by influencing the circulating level of IL-6.
越来越多的证据表明，免疫紊乱和轴突髓鞘形成异常与自闭症谱系障碍（ASD）的病理生理学有关。本研究旨在探讨细胞因子在 ASD 儿童髓鞘损伤中的作用，以及细胞因子失调、髓鞘损伤和细胞因子多态性在 ASD 儿童中的作用。本病例对照研究纳入 98 例 ASD 患儿和 252 例典型发育（TD）对照，采用酶联免疫吸附试验测定血清细胞因子和髓鞘碱性蛋白（MBP）水平。采用聚合酶链反应-限制性片段长度多态性分析方法检测细胞因子多态性。采用儿童自闭症评定量表（CARS）评估自闭症的临床症状。结果显示，与 TD 儿童相比，ASD 患儿血清白细胞介素（IL）-1β、IL-2R、IL-6、IL-8 和 MBP 水平升高。在 ASD 患者中，血清 MBP 水平与 CARS 总分呈显著正相关，血清 IL-1β、IL-2R、IL-6 和 MBP 水平呈正相关。研究数据表明，IL-6MBP 是影响 ASD 发病风险的因素，IL-2RMBP 是影响症状严重程度的因素，可辅助 ASD 的诊断。IL-6-572CC 基因型的存在与血清 IL-6 和 MBP 水平显著升高有关，但不影响 ASD 的发病风险和症状严重程度。因此，这些结果提示 ASD 患儿存在炎症反应和髓鞘损伤。细胞因子失调影响 ASD 中的髓鞘损伤；此外，细胞因子与髓鞘损伤的相互作用影响 ASD 的发病风险和症状严重程度。IL-6-572C/G 基因型可能通过影响 IL-6 的循环水平与 ASD 中的髓鞘损伤有关。
