Medical School of Chinese PLA, Beijing, China.
Faculty of Pediatrics, Chinese PLA General Hospitalgrid.414252.4, Department of Pediatrics, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Microbiol Spectr. 2022 Jun 29;10(3):e0186421. doi: 10.1128/spectrum.01864-21. Epub 2022 Apr 25.
Autism spectrum disorder (ASD), a highly hereditary and heterogeneous neurodevelopmental disorder, is influenced by genetic and environmental factors. Tuberous sclerosis complex (TSC) is a common syndrome associated with ASD. Cytomegalovirus (CMV) infection is an environmental risk factor for ASD. The similarities in pathological and mechanistic pathways of TSC and CMV intrigued us to investigate whether CMV and TSC interacted in ASD's occurrence. We detected CMV IgG seroprevalence of 308 TSC patients from our prospective cohort (September 2011 to March 2021) and 93 healthy children by magnetic particle indirect chemiluminescence immunoassay. A total of 206 TSC patients enrolled were divided into ASD and non-ASD groups, and the relationship between ASD and CMV seroprevalence was analyzed. Nested PCR and Western blot were used to detect CMV DNAs and proteins in cortical malformations of seven TSC patients with and without ASD. No difference was found in CMV seroprevalence between TSC patients and healthy children (74.0% versus 72.0%, = 0.704). Univariate analysis showed the seroprevalence in TSC patients with ASD was higher than that in TSC patients without ASD (89.2% versus 75.1%, = 0.063), and multifactorial analysis showed that CMV seroprevalence was a risk factor for ASD in TSC patients (OR = 3.976, 95% CI = 1.093 to 14.454). Moreover, CMV was more likely to be detected in the cortical malformations in TSC patients with ASD but not in those without ASD. The findings demonstrated that CMV may increase the susceptibility of TSC to ASD. CMV is an environmental risk factor for ASD, but its role in syndromic autism with known genetic etiology has been rarely studied. The pathogenesis of ASD is related to the interaction between environmental and genetic factors. This study demonstrated that CMV can contribute to the occurrence of ASD related to TSC, a common genetic syndrome associated with ASD. Our findings provided support for the theory of gene-environment interaction (G × E) in pathogenesis of ASD and a new perspective for the prevention and therapy for TSC related ASD.
自闭症谱系障碍 (ASD) 是一种高度遗传性和异质性的神经发育障碍，受遗传和环境因素的影响。结节性硬化症 (TSC) 是一种与 ASD 相关的常见综合征。巨细胞病毒 (CMV) 感染是 ASD 的环境危险因素。TSC 和 CMV 在病理和机制途径上的相似性引起了我们的兴趣，我们想研究 CMV 和 TSC 是否在 ASD 的发生中相互作用。我们通过磁微粒化学发光免疫法检测了我们前瞻性队列中的 308 名 TSC 患者（2011 年 9 月至 2021 年 3 月）和 93 名健康儿童的 CMV IgG 血清阳性率。共纳入 206 名 TSC 患者，分为 ASD 组和非 ASD 组，分析 ASD 与 CMV 血清阳性率的关系。巢式 PCR 和 Western blot 用于检测 7 名有和无 ASD 的 TSC 患者皮质畸形中的 CMV DNA 和蛋白质。TSC 患者与健康儿童的 CMV 血清阳性率无差异（74.0%与 72.0%， = 0.704）。单因素分析显示，ASD 组 TSC 患者的血清阳性率高于非 ASD 组 TSC 患者（89.2%与 75.1%， = 0.063），多因素分析显示 CMV 血清阳性率是 TSC 患者 ASD 的危险因素（OR = 3.976，95%CI=1.093 至 14.454）。此外，CMV 更有可能在 ASD 组 TSC 患者的皮质畸形中被检测到，而在非 ASD 组 TSC 患者中则不然。研究结果表明，CMV 可能增加 TSC 发生 ASD 的易感性。CMV 是 ASD 的环境危险因素，但在已知具有遗传病因的综合征性自闭症中的作用很少被研究。ASD 的发病机制与环境和遗传因素的相互作用有关。这项研究表明，CMV 可能导致与 TSC 相关的 ASD 发生，TSC 是一种与 ASD 相关的常见遗传综合征。我们的研究结果为 ASD 发病机制中的基因-环境相互作用（G × E）理论提供了支持，为 TSC 相关 ASD 的预防和治疗提供了新的视角。
