Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?
Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?
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检测血液中的聚糖脱落：新的多发性硬化症生物标志物？
DOI：
10.3389/fimmu.2018.01254
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发表时间：
2018
影响因子：
7.3
通讯作者：
Hempel C
中科院分区：
文献类型：
--
作者：
DellaValle B;Manresa-Arraut A;Hasseldam H;Stensballe A;Rungby J;Larsen A;Hempel C
多发性硬化症（MS）是一种毁灭性的自身免疫性疾病，在人们的生命的黄金时期折磨人们。目前，在最初的临床表现后，没有可靠的标志物来判断患者是否会发展为MS，或者他们的预后是侵袭性的还是复发缓解性的。此外，许多MS患者对治疗没有反应。因此，缺乏疾病的诊断、预后和治疗反应性的标志物，而精确的医学方法将是有价值的。糖萼（GLX）是血管壁富含碳水化合物的外表面，是血液和血管之间的第一次相互作用。我们假设GLX的裂解可能是MS中免疫攻击、血脑屏障（BBB）破坏和疾病严重程度的早期预测因子。本研究包括MS的两种实验模型，实验性自身免疫性脑炎（EAE）。在C57 BL/6 J小鼠和刘易斯大鼠中诱导EAE，监测其与健康对照相比的体重减轻和临床表现。从小鼠中纵向获得血浆样品，直至疾病严重程度峰值和大鼠中处于疾病严重程度峰值。在血浆样本中检测到可溶性GLX相关糖胺聚糖（GAG）和蛋白聚糖（PG）。所有接受EAE乳剂的动物均发生暴发性EAE（100%复发率）。在临床症状出现之前检测到血浆硫酸软骨素水平升高，并在疾病严重程度峰值时保持升高。透明质酸在疾病高峰期增加，而硫酸乙酰肝素仅在早期短暂增加。相比之下，syndecans 1，3和4在EAE样本以及健康对照中检测到，两组之间没有显著差异。在这项研究中，我们提出的数据支持脱落的GLX作为一个新的类MS的生物标志物。特别是，可溶性，糖基GLX组件与疾病的严重程度在两个模型的MS，分子将不会检测到基于蛋白质组学的屏幕MS患者样本。患者研究目前正在进行中。
Multiple sclerosis (MS) is a devastating autoimmune disease, afflicting people in the prime of their lives. Presently, after initial clinical presentation, there are no reliable markers for whether a patient will develop MS, or whether their prognosis will be aggressive or relapsing–remitting. Furthermore, many MS patients do not respond to treatment. Thus, markers for diagnosis, prognosis, and treatment-responsiveness are lacking for a disease, where a precision medicine approach would be valuable. The glycocalyx (GLX) is the carbohydrate-rich outer surface of the blood vessel wall and is the first interaction between the blood and the vessel. We hypothesized that cleavage of the GLX may be an early stage predictor of immune attack, blood–brain barrier (BBB) breakdown, and disease severity in MS. Two experimental models of MS, experimental autoimmune encephalitis (EAE), were included in this study. EAE was induced in C57BL/6J mice and Lewis rats, which were monitored for weight loss and clinical presentation in comparison to healthy controls. Plasma samples were obtained longitudinally from mice until peak disease severity and at peak disease severity in rats. Soluble GLX-associated glycosaminoglycans (GAG) and proteoglycans (PG) were detected in plasma samples. All animals receiving EAE emulsion developed fulminant EAE (100% penetrance). Increased plasma levels of chondroitin sulfate were detected before the onset of clinical symptoms and remained elevated at peak disease severity. Hyaluronic acid was increased at the height of the disease, whereas heparan sulfate was transiently increased during early stages only. By contrast, syndecans 1, 3, and 4 were detected in EAE samples as well as healthy controls, with no significant differences between the two groups. In this study, we present data supporting the shedding of the GLX as a new class of biomarker for MS. In particular, soluble, sugar-based GLX components are associated with disease severity in two models of MS, molecules that would not be detected in proteomics-based screens of MS patient samples. Patient studies are presently underway.
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影响因子：
4.5
作者：
Reitsma, Sietze;Slaaf, Dick W.;Vink, Hans;van Zandvoort, Marc A. M. J.;Egbrink, Mirjam G. A. oude
通讯作者：
Egbrink, Mirjam G. A. oude
DOI：
10.1016/s1474-4422(17)30299-5
发表时间：
2017-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
GBD 2015 Neurological Disorders Collaborator Group
通讯作者：
GBD 2015 Neurological Disorders Collaborator Group
DOI：
10.1056/nejmra1401483
发表时间：
2018-01-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Reich DS;Lucchinetti CF;Calabresi PA
通讯作者：
Calabresi PA
影响因子：
16.6
作者：
Keough MB;Rogers JA;Zhang P;Jensen SK;Stephenson EL;Chen T;Hurlbert MG;Lau LW;Rawji KS;Plemel JR;Koch M;Ling CC;Yong VW
通讯作者：
Yong VW
DOI：
10.1186/s13054-015-0741-z
发表时间：
2015-01-28
期刊：
Critical care (London, England)
影响因子：
--
作者：
Chelazzi C;Villa G;Mancinelli P;De Gaudio AR;Adembri C
通讯作者：
Adembri C