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自闭症谱系障碍中的细胞因子表达谱:来自土耳其的一项多中心研究。

Cytokine expression profiles in Autism spectrum disorder: A multi-center study from Turkey.

机构信息

Department of Child and Adolescent Psychiatry, Baskent University, Dr. Turgut Noyan Medical and Research Center, Adana, Turkey.

Department of Child and Adolescent Psychiatry, Acibadem Mehmet Ali Aydinlar University, İstanbul, Turkey.

出版信息

Cytokine. 2020 Sep;133:155152. doi: 10.1016/j.cyto.2020.155152. Epub 2020 Jun 18.

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in communication and social interaction as well as restricted interests and repetitive behaviors. The pathogenesis of ASD is not completely understood, but a growing body of research has demonstrated that the immune response may be a contributing factor in the etiology and/ or ontogeny of ASD. The aim of this study was to determine the expression levels of IL-1β, IL-1α, IL-4, IL-6, IL-17, TNF-α and TGF-β in peripheral blood mononuclear cells of children with ASD and healthy controls in order to determine the contributions of cytokines to ASD. Within the study timeframe, 195 children with ASDs (80.5% male) and 162 controls (73.6% male) were enrolled. Most children with ASD had a comorbid disorder (n = 114, 58.5%), with the most common diagnoses as Intellectual Developmental Disorder (IDD, n = 64, 32.8%) and ADHD (n = 64, 32.8%). The majority of children with ASD had severe autistic symptoms as evaluated via Childhood Autism Rating Scale (CARS, n = 130, 64.6%). The mean CARS score in the ASD sample was 40.8 (S.D. = 7.6). The patients with ASD were found to have significantly higher levels of IL-6 (p < 0.001) and significantly lower levels of IL-17 (p < 0.05, all Bonferroni corrected). Treatment tended to affect IL-4 levels. Lastly, discriminant function analysis (DFA) revealed that a combination of IL-6, IL-17 and IL-1α correctly classified 56.6% of cases. Despite extensive immunological evidence suggesting immune system aberrations, further research is required to clarify the relationship between immune profiles and ASD symptoms.

摘要

自闭症谱系障碍 (ASD) 是一种复杂的神经发育障碍,其特征是在沟通和社交互动方面存在障碍,以及兴趣受限和重复行为。ASD 的发病机制尚不完全清楚,但越来越多的研究表明,免疫反应可能是 ASD 的病因和/或发病机制的一个促成因素。本研究旨在确定自闭症谱系障碍儿童和健康对照者外周血单个核细胞中白细胞介素-1β (IL-1β)、白细胞介素-1α (IL-1α)、白细胞介素-4 (IL-4)、白细胞介素-6 (IL-6)、白细胞介素-17 (IL-17)、肿瘤坏死因子-α (TNF-α) 和转化生长因子-β (TGF-β) 的表达水平,以确定细胞因子对 ASD 的贡献。在研究期间,共纳入 195 名自闭症谱系障碍儿童 (80.5%为男性) 和 162 名对照者 (73.6%为男性)。大多数自闭症谱系障碍儿童存在共患疾病 (n=114,58.5%),最常见的诊断为智力发育障碍 (n=64,32.8%) 和注意缺陷多动障碍 (n=64,32.8%)。大多数自闭症谱系障碍儿童的自闭症症状严重,采用儿童自闭症评定量表 (CARS) 评估,有 130 名儿童 (64.6%) 为严重自闭症。自闭症组的平均 CARS 评分为 40.8(标准差=7.6)。结果发现,自闭症组患者的白细胞介素-6(IL-6)水平显著升高(p<0.001),白细胞介素-17(IL-17)水平显著降低(p<0.05,均经 Bonferroni 校正)。治疗有影响白细胞介素-4(IL-4)水平的趋势。最后,判别函数分析(DFA)显示,IL-6、IL-17 和 IL-1α 的组合正确分类了 56.6%的病例。尽管有大量免疫方面的证据表明免疫系统异常,但仍需要进一步研究以阐明免疫特征与自闭症症状之间的关系。

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