Differences in Intercellular Communication During Clinical Relapse and Gadolinium-Enhanced MRI in Patients With Relapsing Remitting Multiple Sclerosis: A Study of the Composition of Extracellular Vesicles in Cerebrospinal Fluid.
Differences in Intercellular Communication During Clinical Relapse and Gadolinium-Enhanced MRI in Patients With Relapsing Remitting Multiple Sclerosis: A Study of the Composition of Extracellular Vesicles in Cerebrospinal Fluid.
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DOI：
10.3389/fncel.2018.00418
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发表时间：
2018
影响因子：
5.3
通讯作者：
Salemi G
中科院分区：
文献类型：
--
作者：
Geraci F;Ragonese P;Barreca MM;Aliotta E;Mazzola MA;Realmuto S;Vazzoler G;Savettieri G;Sconzo G;Salemi G
本研究基于这样一种假设：从脑脊液中分离的细胞外小泡(EV)的水平和表面标志表达的变化可能与多发性硬化(MS)的临床形式、疾病活动性和严重程度有关。这些分析是在患有多发性硬化症或其他神经疾病的受试者身上进行的。用流式细胞仪对超速离心法分离的EVS进行鉴定。一组荧光抗体被用来鉴定EV的来源：CD4、CCR3、CCR5、CD19和CD200，以及异凝素IB4。统计分析采用Mann-Whitney U检验和Kruskal-Wallis检验。在进展性多发性硬化症患者和临床孤立综合征患者中，从脑脊液中分离出的EVS比所有其他被检查的组都要丰富。此外，在MS的活动期，EV的数量及其表面标志的表达发生了重要的变化[即临床复发和磁共振成像(MRI)上出现强化病变]。特别是，在临床复发期间，受MS影响的患者的CSF-EV数量增加；这一发现与CD19+/CD200+(幼稚B细胞)EV数量的减少有关。这些标记物由未成熟和幼稚的B淋巴细胞表达，据我们所知，这种双重染色从未与MS有关，但在另一种类型的Th1细胞介导的自身免疫病患者中观察到它们的减少。相比之下，Gd增强MRI显示的脑和脊柱病变与CCR3+/CCR5+(CD8记忆T细胞亚群)、CD4+/CCR3+(Th2细胞)和CD4+/CCR5+(Th1细胞)CSF-EV的数量增加有关。有两点值得强调：(I)本研究中获得的数据证实，CSF-EVS是一种潜在的有前景的工具，可用于识别MS不同阶段的特定生物标志物；(Ii)考虑到EVS在细胞间通讯中的作用，我们的结果提供了一些见解，有助于我们更好地理解MS发病机制中主要涉及的一些细胞类型(如淋巴细胞、胶质细胞和神经元)之间的关系。
This study was designed based on the hypothesis that changes in both the levels and surface marker expression of extracellular vesicles (EVs) isolated from the cerebrospinal fluid (CSF) may be associated with the clinical form, disease activity, and severity of multiple sclerosis (MS). The analyzes were performed on subjects affected by MS or other neurological disorders. EVs, which were isolated by ultracentrifugation of CSF samples, were characterized by flow cytometry. A panel of fluorescent antibodies was used to identify the EV origin: CD4, CCR3, CCR5, CD19, and CD200, as well as isolectin IB4. The Mann–Whitney U-test and Kruskal–Wallis test were used for statistical analyzes. EVs isolated from the CSF were more abundant in patients with progressive MS and in those with a clinically isolated syndrome than in all the other groups examined. Furthermore, an important change in the number of EVs and in their surface marker expression occurred during active phases of MS [i.e., clinical relapses and the presence of enhancing lesions on magnetic resonance imaging (MRI)]. In particular, the number of CSF-EVs increased in patients affected by MS during clinical relapse; this finding was associated with a decrease in the number of CD19+/CD200+ (naïve B cells) EVs. These markers are expressed by immature and naïve B lymphocytes, and to the best of our knowledge, this double staining has never been associated with MS, but their reduction has been observed in patients with another type of Th1 cell-mediated autoimmune disease. In contrast, the presence of lesions in the brain and spine on gadolinium-enhanced MRI was associated with an increase in the numbers of CCR3+/CCR5+ (subset of CD8 memory T cells), CD4+/CCR3+ (Th2 cells), and CD4+/CCR5+ (Th1 cells) CSF-EVs. Two points are worth emphasizing: (i) the data obtained in this study confirm that CSF-EVs represent a potentially promising tool to identify biomarkers specific for different phases of MS; and (ii) Considering the role of EVs in intercellular communication, our results provide some insights that improve our understanding of the relationships among some of the cell types that are mainly involved in MS pathogenesis (e.g., lymphocytes, glia, and neurons).
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影响因子：
9.3
作者：
Bassi, Mario Stampanoni;Iezzi, Ennio;Buttari, Fabio
通讯作者：
Buttari, Fabio
影响因子：
11.1
作者：
Baker D;Marta M;Pryce G;Giovannoni G;Schmierer K
通讯作者：
Schmierer K
影响因子：
6.7
作者：
Connor, David Ewan;Exner, Thomas;Joseph, Joanne Emily
通讯作者：
Joseph, Joanne Emily
影响因子：
15.3
作者：
Bonecchi, R;Bianchi, G;Bordignon, P P;D'Ambrosio, D;Lang, R;Borsatti, A;Sozzani, S;Allavena, P;Gray, P A;Mantovani, A;Sinigaglia, F
通讯作者：
Sinigaglia, F
DOI：
10.1084/jem.192.3.393
发表时间：
2000-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Babbe H;Roers A;Waisman A;Lassmann H;Goebels N;Hohlfeld R;Friese M;Schröder R;Deckert M;Schmidt S;Ravid R;Rajewsky K
通讯作者：
Rajewsky K