Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis.
Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis.
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脑脊液标记物显示出进行性多发性硬化症的鞘内炎症。
DOI：
10.1002/ana.24408
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发表时间：
2015-07
影响因子：
11.2
通讯作者：
Bielekova B
中科院分区：
文献类型：
--
作者：
Komori M;Blake A;Greenwood M;Lin YC;Kosa P;Ghazali D;Winokur P;Natrajan M;Wuest SC;Romm E;Panackal AA;Williamson PR;Wu T;Bielekova B
由于无法可靠地测量鞘内炎症，对复杂的神经免疫疾病患者的管理受到阻碍。目前实施的实验室测试是40年前开发的，要么不是动态的，要么不能捕获低水平的中枢神经系统（CNS）炎症。因此，我们的目标是在2个盲法、前瞻性获得的未治疗的神经免疫疾病患者和嵌入对照组中识别和验证中枢神经系统炎症的生物标志物，最终目标是开发临床有用的工具。由于效用最大的生物标志物反映了免疫表型，我们纳入了纯化的原代免疫细胞的细胞特异性评估。通过优化的电化学发光免疫分析法对生物标志物进行定量。在细胞特异性分泌的标志物中，可溶性CD27是鞘内t细胞活化的有效生物标志物，受体工作特征曲线下面积为0.97。比较脑脊液（CSF）免疫细胞的数量及其各自的细胞特异性可溶性生物标志物（由CSF细胞及其在中枢神经系统组织中的对应物释放）提供了关于静止中枢神经系统免疫反应的宝贵信息，以前只能通过脑活检获得。出乎意料的是，进行性和复发缓解型多发性硬化症（MS）患者有相当数量的激活鞘内T细胞和B细胞，前者优先嵌入中枢神经系统组织。鞘内炎症的细胞特异性生物标志物可以改善神经免疫疾病的诊断和管理，并为未被成像捕获的鞘内炎症患者（如进展性多发性硬化症）的未来治疗发展提供药效学标志物。
The management of complex patients with neuroimmunological diseases is hindered by an inability to reliably measure intrathecal inflammation. Currently implemented laboratory tests developed >40 years ago either are not dynamic or fail to capture low levels of central nervous system (CNS) inflammation. Therefore, we aimed to identify and validate biomarkers of CNS inflammation in 2 blinded, prospectively acquired cohorts of untreated patients with neuroimmunological diseases and embedded controls, with the ultimate goal of developing clinically useful tools. Because biomarkers with maximum utility reflect immune phenotypes, we included an assessment of cell specificity in purified primary immune cells. Biomarkers were quantified by optimized electrochemiluminescent immunoassays. Among markers with cell-specific secretion, soluble CD27 is a validated biomarker of intrathecal T-cell activation, with an area under the receiver operating characteristic curve of 0.97. Comparing the quantities of cerebrospinal fluid (CSF) immune cells and their respective cell-specific soluble biomarkers (released by CSF cells as well as their counterparts in CNS tissue) provided invaluable information about stationary CNS immune responses, previously attainable via brain biopsy only. Unexpectedly, progressive and relapsing–remitting multiple sclerosis (MS) patients have comparable numbers of activated intrathecal T and B cells, which are preferentially embedded in CNS tissue in the former group. The cell-specific biomarkers of intrathecal inflammation may improve diagnosis and management of neuroimmunological diseases and provide pharmacodynamic markers for future therapeutic developments in patients with intrathecal inflammation that is not captured by imaging, such as in progressive MS.
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影响因子：
2.5
作者：
Bonnan M
通讯作者：
Bonnan M
DOI：
10.4049/jimmunol.1302884
发表时间：
2014-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Han S;Lin YC;Wu T;Salgado AD;Mexhitaj I;Wuest SC;Romm E;Ohayon J;Goldbach-Mansky R;Vanderver A;Marques A;Toro C;Williamson P;Cortese I;Bielekova B
通讯作者：
Bielekova B
影响因子：
9.1
作者：
Desplat-Jégo, S;Feuillet, L;Boucraut, J
通讯作者：
Boucraut, J
影响因子：
11.2
作者：
HAUSER, SL;BHAN, AK;WEINER, HL
通讯作者：
WEINER, HL
衰老大脑中的小胶质细胞：与神经退行性变的相关性
影响因子：
15.1
作者：
Luo XG;Ding JQ;Chen SD
通讯作者：
Chen SD