PDF(Pubmed)
Abstract：
Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1β), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1β, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved.
摘要：
自闭症谱系障碍（ASD）与多种生理异常有关。目前的实验室和临床证据最常报告线粒体功能障碍，氧化应激，以及身体几乎所有细胞类型的免疫失衡。本工作旨在评估耗氧率(OCR)，细胞外酸化率（ECAR），和炎症相关分子，如环氧合酶-2（COX-2），几丁质酶3样蛋白1（YKL-40），白细胞介素-1β（IL-1β），与健康对照相比，有和没有消退的ASD儿童中的白细胞介素-9（IL-9）。患有ASD的儿童(n=56)和通常发育中的儿童(TDC，n=12），年龄为1.11至11岁。从ASD儿童和对照组分离的外周血单核细胞（PBMC）中检查线粒体活性，使用代谢分析仪。IL-1β的基因和蛋白水平,平行研究IL-9、COX-2和YKL-40。我们的结果表明，消退患者的ASD亚组的PBMC(ASDR(+)，n=21）具有线粒体活动的特定模式，最大呼吸显着增加，呼吸备用容量，和质子泄漏与非回归基团(ASDR(-)，n=35）和TDC。此外，我们发现所研究的促炎分子不平衡,ASDR(-)水平升高,证明与炎症改变有关.这项研究的结果为ASD中免疫细胞的特定生物能量谱和炎症相关分子的升高提供了新的证据。第一次,提供了ASDR（）中独特代谢谱的数据，并将其与年龄和性别相似的随机儿童组进行了比较。我们的数据表明，线粒体功能障碍在ASDR(+)中更为显著，而在ASD中，R（-）炎症更为明显。可能,在没有回归的组中，免疫机制(免疫失调，导致炎症)最初开始，后期线粒体活性也受到外源因素的影响。另一方面,在回归组中，最初的损伤是在线粒体，并且可能在后期涉及免疫功能障碍。
