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分析可溶性白细胞介素-2 受体作为神经结节病的 CSF 生物标志物。

Analysis of soluble interleukin-2 receptor as CSF biomarker for neurosarcoidosis.

机构信息

From the Department of Neurology (C.O., O.W., K.R.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Labor Berlin Charité-Vivantes GmbH (N.U., C.M.); and Institute for Medical Immunology (C.M.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2020 May 11;7(4). doi: 10.1212/NXI.0000000000000725. Print 2020 Jul.

Abstract

OBJECTIVE

To systematically analyze soluble interleukin-2 receptor (sIL-2R) in CSF as a diagnostic and disease activity biomarker in patients with sarcoidosis involving the CNS (neurosarcoidosis).

METHODS

sIL-2R was determined by chemiluminescent immunoassays in CSF/serum samples from patients with neurosarcoidosis (n = 23), MS (n = 19), neurotuberculosis (n = 8), viral (n = 18) and bacterial (n = 9) meningitis, cerebral lymphoma (n = 15), Guillain-Barré syndrome (n = 8), and 115 patients with noninflammatory neurologic diseases (NINDs) as controls. The sIL-2R index was calculated by dividing the CSF/serum sIL-2R quotient (Q) through the CSF/serum albumin quotient (Q). sIL-2R quotient diagrams were established by plotting Q against Q. sIL-2R levels were correlated with clinical, MRI, and CSF disease activity markers of neurosarcoidosis.

RESULTS

Patients with neurosarcoidosis had higher CSF sIL-2R, Q, and sIL-2R index values than patients with NINDs ( < 0.0001 for all pairwise group comparisons). sIL-2R quotient diagrams demonstrated an intrathecal sIL-2R synthesis in >50% of neurosarcoidosis samples. Similar findings were observed in viral/bacterial meningitis, CNS lymphoma, and, most pronounced, in neurotuberculosis, but not in patients with MS. CSF sIL-2R parameters were associated with clinical disease activity, leptomeningeal gadolinium enhancement, and the CSF white cell count in patients with neurosarcoidosis.

CONCLUSIONS

CSF sIL-2R parameters are elevated in patients with neurosarcoidosis, but this finding is not specific for neurosarcoidosis. Nevertheless, CSF sIL-2R parameters may help distinguishing neurosarcoidosis from MS and are associated with clinical, radiologic, and CSF disease activity markers of neurosarcoidosis.

CLASSIFICATION OF EVIDENCE

This study provides Class II evidence that CSF sIL-2R parameters distinguish neurosarcoidosis from NINDs and MS.

摘要

目的

系统分析脑脊液中可溶性白细胞介素 2 受体 (sIL-2R) 作为累及中枢神经系统(神经结节病)的结节病患者的诊断和疾病活动生物标志物。

方法

采用化学发光免疫分析法检测神经结节病患者(n=23)、多发性硬化症(MS)患者(n=19)、结核性脑膜炎(n=8)、病毒性(n=18)和细菌性(n=9)脑膜炎、脑淋巴瘤(n=15)、格林-巴利综合征(n=8)以及 115 例非炎症性神经疾病患者(NINDs)的脑脊液/血清样本中的 sIL-2R。通过将脑脊液/血清 sIL-2R 商(Q)除以脑脊液/血清白蛋白商(Q)计算 sIL-2R 指数。通过绘制 Q 与 Q 的关系图建立 sIL-2R 商图。sIL-2R 水平与神经结节病的临床、MRI 和脑脊液疾病活动标志物相关。

结果

与 NINDs 患者相比,神经结节病患者的脑脊液 sIL-2R、Q 和 sIL-2R 指数值更高(所有两两比较组间差异均<0.0001)。sIL-2R 商图显示超过 50%的神经结节病样本存在鞘内 sIL-2R 合成。在病毒性/细菌性脑膜炎、中枢神经系统淋巴瘤中也观察到类似的发现,且在结核性脑膜炎中最为明显,但在 MS 患者中则不然。在神经结节病患者中,脑脊液 sIL-2R 参数与临床疾病活动、软脑膜钆增强以及脑脊液白细胞计数相关。

结论

神经结节病患者的脑脊液 sIL-2R 水平升高,但这一发现并不能特异性地诊断神经结节病。然而,脑脊液 sIL-2R 水平可能有助于将神经结节病与 MS 相鉴别,且与神经结节病的临床、影像学和脑脊液疾病活动标志物相关。

证据分类

本研究提供了 II 级证据,表明脑脊液 sIL-2R 水平可用于区分神经结节病与 NINDs 和 MS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80e1/7238895/7babaf68a5b4/NEURIMMINFL2019025692f1.jpg

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