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自闭症患者外周血单个核细胞中miR-181b-5p、miR-23a-3p、BCL-2和IL-6的评估;可靠生物标志物的可能性

Assessment of miR-181b-5p, miR-23a-3p, BCL-2, and IL-6 in Peripheral Blood Mononuclear Cells of Autistic Patients; Likelihood of Reliable Biomarkers.

作者信息

Atwan Hossein, Assarehzadegan Mohammad-Ali, Shekarabi Mehdi, Jazayeri Seyed Mohammad, Barfi Shahram, Shokouhi Shoormasti Raheleh, Chimeh Narges, Pouretemad Hamid Reza, Tayebi Behnoosh

机构信息

Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2020 Feb 1;19(1):74-83. doi: 10.18502/ijaai.v19i1.2420.

Abstract

Autism is a neurodevelopmental disorder that is recognized by stereotypic and repetitive behaviors after 2 years of old. Dysregulation of the immune system, especially inflammation which is mostly regulated by IL-6, imposes a deficit in CNS development. Along with this crucial biomarker, researchers have proposed BCL-2, micro RNA-23a-3p (miR-23a-3p), miR-181b-5p as other probable biomarkers involved in inflammation and apoptosis. The aim of the study was to evaluate the alteration in the expression of these biomarkers in a group of autism spectrum disorder (ASD) children. Peripheral blood mononuclear cells (PBMCs) were obtained from 37 autistic patients. After RNA extraction with precipitation method, the Syber green qReal-time Polymerase Chain Reaction (PCR) was performed in order to evaluate the possible alteration in the expression of IL-6, BCL-2, miR-181b-5p, and miR-23a-3p. The results were compared with healthy controls. IL-6 was significantly upregulated in ASD patients (p=0.003). On the other hand, miR-23a was upregulated and BCL-2 downregulated in ASD patients but the changes were not significant. In initial evaluations, expression changes of miR-181b-5p were not statistically significant. However, when Patients were divided into two groups of upregulated and downregulated, re-evaluation showed that both up- (p=0.005) and down-regulation (p=0.004) (i.e. changes regardless of the direction) of miR-181b were significant in autistic children. IL-6 and miR-181b-5p can have proper diagnostic values and are reliable biomarkers with high sensitivity and specificity. On the other hand, PBMC can be utilized for such studies and also evaluation of patients' condition instead of brain tissue as it is less accessible.

摘要

自闭症是一种神经发育障碍,在2岁后会表现出刻板和重复行为。免疫系统失调,尤其是主要由白细胞介素-6(IL-6)调节的炎症,会导致中枢神经系统发育缺陷。除了这个关键生物标志物外,研究人员还提出BCL-2、微小RNA-23a-3p(miR-23a-3p)、miR-181b-5p作为参与炎症和细胞凋亡的其他可能生物标志物。本研究的目的是评估一组自闭症谱系障碍(ASD)儿童中这些生物标志物表达的变化。从37名自闭症患者中获取外周血单个核细胞(PBMC)。采用沉淀法提取RNA后,进行荧光定量聚合酶链反应(qReal-time PCR)以评估IL-6、BCL-2、miR-181b-5p和miR-23a-3p表达的可能变化。将结果与健康对照进行比较。ASD患者中IL-6显著上调(p = 0.003)。另一方面,ASD患者中miR-23a上调而BCL-2下调,但变化不显著。在初步评估中,miR-181b-5p的表达变化无统计学意义。然而,当将患者分为上调和下调两组时,重新评估显示,miR-181b在自闭症儿童中的上调(p = 0.005)和下调(p = 0.004)(即无论变化方向)均具有统计学意义。IL-6和miR-181b-5p可具有适当的诊断价值,是具有高敏感性和特异性的可靠生物标志物。另一方面,PBMC可用于此类研究以及评估患者病情,而无需使用难以获取的脑组织。

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