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神经发育障碍的综合免疫分析表明,基于增加的神经发生,Th-1极化或IL-1信号传递的三个不同的类别

Nikhitha Sreenivas¹, Michael Maes², Hansashree Padmanabha³

¹Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India.

Brain, behavior, and immunity

|November 16, 2023

概括

神经发育障碍 (NDD) 具有共同的免疫系统异常,包括改变的互白素信号传递和巨细胞两极分化. 机器学习在NDD中确定了不同的免疫特征,表明了潜在的新药标.

科学领域:

免疫学免疫学免疫学
神经科学是一个神经科学.
遗传学遗传学是一个

背景情况:

神经发育障碍 (NDDs) 涵盖了一系列具有重叠但独特特征的疾病.
免疫失调越来越被认为是NDD的重要因素.
不同NDD的特定共享免疫病原遗传机制在很大程度上仍未被探索.

研究的目的:

调查潜在的共同免疫病因,这三种早期发病的NDDs的潜在共同免疫病因:自闭症谱系障碍 (ASD),注意力缺陷多动性障碍 (ADHD) 和智力障碍障碍 (IDD).
分析免疫特征,并确定这些NDD之间的共享或独特的免疫特征.

主要方法:

从135名患有NDD的儿童 (每个有45名ASD,ADHD,IDD) 和35名典型发育儿童的血中测试了48个与免疫通路相关的标志物.
使用多重悬浮试验与Pro人类细胞因子48-plex套件.
应用机器学习算法来分析免疫标记水平并分类NDD子组.

主要成果:

NDDs表现出一个耗尽的补偿性免疫调节系统 (CIRS),增加了互白素-1 (IL-1) 信号发送,提高了IL-4和CCL2水平,以及改变了巨细胞两极分化.
鉴定了对NDDs具有高灵敏度 (81.8%) 和特异性的免疫异常 (94.4%).
机器学习揭示了NDD群体内的三种不同的免疫群,其特点是增强的神经发生,Th-1极化或IL-1信号传递.

结论:

ASD,ADHD和IDD共享显著的免疫异常,在特定的细胞因子 (IL-9,IL-17,CCL12) 中存在微小的差异.
在NDD中免疫失调会影响神经发生,神经毒性和整体神经发育.
基于独特的免疫特征的亚组分类为NDD治疗中提供了新的治疗点的潜力.

关键词:

注意缺陷多动性障碍注意缺陷多动性障碍自闭症谱系障碍自闭症谱系障碍生物标志物生物标志物炎症炎症是一种炎症.智力障碍障碍是一种精神障碍.心理健康心理健康神经发育神经发育神经发育障碍神经发育障碍神经科学是一个神经科学.精神病学是一个精神病学.共同的病因学是共享的.

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