Ashwood Paul
Department of Medical Microbiology and Immunology, School of Medicine, MIND Institute, University of California Davis, Davis, CA 95616, USA.
Biomedicines. 2023 Feb 2;11(2):436. doi: 10.3390/biomedicines11020436.
Autism spectrum disorder (AU) is present in approximately 2% of the population and is often associated with co-morbidities that can impact quality of life. One of the most common co-morbidities in autism is the presence of gastrointestinal (GI) symptoms consisting of irregular bowel habits such as constipation, diarrhea, or alternating bowel habit. Evidence of immune infiltration and immune activation has been shown in the ileum and colon of children with AU with GI symptoms. Moreover, immune dysfunction is a contributing factor in many GI diseases, and we hypothesize that it would be more apparent in children with AU that exhibit GI symptoms than those who do not present with GI symptoms. The aim of this preliminary study was to determine whether there are altered cytokine levels in plasma in children with AU with GI symptoms compared with children with AU without GI symptoms, typically developing (TD) children with GI symptoms and TD children without GI symptoms, from the same population-based cohort. Plasma cytokine levels were assessed by multiplex assays. No differences in plasma cytokines were observed in TD controls with or without GI symptoms; however, many innate (IL-1α, TNFα, GM-CSF, IFNα) and adaptive cytokines (IL-4, IL-13, IL-12p70) were increased in AU children with GI symptoms compared with children with AU with no GI symptoms. The mucosal relevant cytokine IL-15 was increased in AU with GI symptoms compared with all groups. In contrast, the regulatory cytokine IL-10, was reduced in AU with GI symptoms and may suggest an imbalance in pro-inflammatory/regulatory signals. These data suggest that children with AU and GI symptoms have an imbalance in their immune response that is evident in their circulating plasma cytokine levels. A finding that could point to potential therapeutic and/or monitoring strategies for GI issues in AU.
自闭症谱系障碍(AU)在大约2%的人群中存在,并且常常与会影响生活质量的共病相关。自闭症最常见的共病之一是胃肠道(GI)症状的出现,包括便秘、腹泻或排便习惯交替等肠道习惯不规律。有证据表明,患有胃肠道症状的自闭症儿童的回肠和结肠存在免疫浸润和免疫激活。此外,免疫功能障碍是许多胃肠道疾病的一个促成因素,我们推测,与没有胃肠道症状的自闭症儿童相比,有胃肠道症状的自闭症儿童的免疫功能障碍会更明显。这项初步研究的目的是确定,与来自同一人群队列的没有胃肠道症状的自闭症儿童、有胃肠道症状的典型发育(TD)儿童以及没有胃肠道症状的TD儿童相比,有胃肠道症状的自闭症儿童血浆中的细胞因子水平是否存在变化。通过多重检测法评估血浆细胞因子水平。在有或没有胃肠道症状的TD对照组中,未观察到血浆细胞因子有差异;然而,与没有胃肠道症状的自闭症儿童相比,有胃肠道症状的自闭症儿童的许多先天细胞因子(IL-1α、TNFα、GM-CSF、IFNα)和适应性细胞因子(IL-4、IL-13、IL-12p70)有所增加。与所有组相比,有胃肠道症状的自闭症患者中与黏膜相关的细胞因子IL-15有所增加。相比之下,有胃肠道症状的自闭症患者中调节性细胞因子IL-10减少,这可能表明促炎/调节信号失衡。这些数据表明,有胃肠道症状的自闭症儿童的免疫反应存在失衡,这在他们循环血浆细胞因子水平上很明显。这一发现可能为自闭症患者胃肠道问题指明潜在的治疗和/或监测策略。