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.
Neurol Neuroimmunol Neuroinflamm. 2020 May 11;7(4). doi: 10.1212/NXI.0000000000000725. Print 2020 Jul.
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).
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.
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.
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.
This study provides Class II evidence that CSF sIL-2R parameters distinguish neurosarcoidosis from NINDs and MS.
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。
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。
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。
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。
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。