Division of Pediatrics, Chang Gung Memorial Hospital at Taipei, Taipei, Taiwan; Division of Pediatric Neurology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Primary Immunodeficiency Care and Research (PICAR) Institute, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Pediatric Critical Care, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biomed J. 2020 Jun;43(3):293-304. doi: 10.1016/j.bj.2020.05.007. Epub 2020 May 29.
Defective human TLR3 signaling causes recurrent and refractory herpes simplex encephalitis/encephalopathy. Children with febrile infection-related epilepsy syndrome with refractory seizures may have defective TLR responses.
Children with febrile infection-related epilepsy syndrome were enrolled in this study to evaluate TLR1-9 responses (IL-6, IL-8, IL-12p40, INF-α, INF-γ, and TNF-α) in their peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MDDCs), compared to those with febrile seizures and non-refractory epilepsy with/without underlying encephalitis/encephalopathy.
Adenovirus and enterovirus were found in throat cultures of enrolled patients (2-13 years) as well as serologic IgM elevation of mycoplasma pneumonia and herpes simplex virus, although neither detectable pathogens nor anti-neural autoantibodies in the CSF could be noted. Their PBMCs and MDDCs trended to have impaired TLR responses and significantly lower in cytokine profiles of TLR3, TLR4, TLR7/8, and TLR9 responses but not other TLRs despite normal TLR expressions and normal candidate genes for defective TLR3 signaling. They also had decreased naïve T and T regulatory cells, and weakened phagocytosis.
Children with febrile infection-related epilepsy syndrome (FIRES) could have impaired TLR3, TLR4, TLR7/8, and TLR9 responses possibly relating to their weakened phagocytosis and decreased T regulatory cells.
人类 TLR3 信号传导缺陷可导致单纯疱疹性脑炎/脑病反复发作和难治。伴有难治性癫痫发作的发热感染相关癫痫综合征患儿可能存在 TLR 反应缺陷。
本研究纳入发热感染相关癫痫综合征患儿，以评估其外周血单核细胞（PBMC）和单核细胞衍生树突状细胞（MDDC）中的 TLR1-9 反应（IL-6、IL-8、IL-12p40、IFN-α、IFN-γ 和 TNF-α），并与发热性惊厥和无脑炎/脑病的非难治性癫痫患儿进行比较。
纳入的患者（2-13 岁）的咽拭子培养中发现腺病毒和肠道病毒，以及肺炎支原体和单纯疱疹病毒的血清 IgM 升高，但脑脊液中未检测到病原体或神经自身抗体。尽管其 PBMC 和 MDDC 的 TLR 表达正常，且 TLR3 信号传导缺陷的候选基因正常，但 TLR 反应呈受损趋势，且 TLR3、TLR4、TLR7/8 和 TLR9 反应的细胞因子谱明显较低，而其他 TLR 则无明显差异。此外，他们还存在幼稚 T 细胞和 T 调节细胞减少，吞噬作用减弱。
发热感染相关癫痫综合征（FIRES）患儿可能存在 TLR3、TLR4、TLR7/8 和 TLR9 反应受损，这可能与其减弱的吞噬作用和减少的 T 调节细胞有关。
Zotero 插件
