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多发性硬化症和神经白塞病血液及脑脊液中的差异基因表达模式

Differential Gene Expression Patterns in Blood and Cerebrospinal Fluid of Multiple Sclerosis and Neuro-Behçet Disease.

作者信息

Maghrebi Olfa, Hanachi Mariem, Bahrini Khadija, Kchaou Mariem, Jeridi Cyrine, Belal Samir, Ben Sassi Samia, Barbouche Mohamed-Ridha, Souiai Oussama, Belghith Meriam

机构信息

Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, Tunis, Tunisia.

Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia.

出版信息

Front Genet. 2021 Feb 26;12:638236. doi: 10.3389/fgene.2021.638236. eCollection 2021.

Abstract

Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.

摘要

中枢神经系统炎性脱髓鞘疾病是青壮年的致残性疾病,在此我们聚焦于多发性硬化症(MS)和神经白塞病(NBD)。MS是一种中枢神经系统自身免疫性疾病。NBD是一种特发性慢性复发性多系统炎性疾病——白塞病的神经系统表现。MS和NBD的诊断依赖于临床症状、磁共振成像和实验室检查。在初次发病时,这两种疾病在临床和影像学上可能存在相似之处,使得鉴别诊断具有挑战性,并延误了适当的治疗。为了确定额外的鉴别生物标志物模式,我们测量并比较了患有NBD、MS和非炎性神经系统疾病(NIND)的患者血液和脑脊液(CSF)细胞中一组广泛选择基因的基因表达。为实现这一目标,应用了双变量和多变量分析。主成分分析(PCA)突出了NBD、MS和对照组之间的不同特征。血液中的转录因子foxp3以及IL-4、IL-10和IL-17的表达是导致MS和NBD聚类分离的主要参数。此外,CSF中与细胞活化和炎性细胞因子相关的参数在这两种炎性疾病和对照组之间有明显差异。我们进行了ROC分析,以确定这两种炎性神经系统疾病之间最具区别性的参数。后一项分析表明,血液中的IL-17、CD73以及CSF中的IL-1β和IL-10是MS和NBD之间最具鉴别性的参数。我们得出结论,血液和CSF中的联合多维度分析表明,这两种神经炎性疾病的病理生理学受不同机制支配。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e060/7954360/6c5f2658d270/fgene-12-638236-g001.jpg

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