Department of Neurology, Chang Gung Memorial Hospital, Keelung 204, Taiwan.
Department of Hematology and Oncology, Chang Gung Memorial Hospital, Keelung 204, Taiwan; School of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Brain Res. 2023 Dec 15;1821:148587. doi: 10.1016/j.brainres.2023.148587. Epub 2023 Sep 20.
In cases of immune-mediated neurological disorders (IMND), different syndromes are associated with antibodies against neuronal surface antigens, intra-neuronal antigens, astrocytic aquaporin, and gangliosides. These autoantibodies can be pathogenic or connected to neuroinflammation and resulting neuronal injuries. This study aims to identify a blood biomarker that can detect neuronal damage in individuals with IMND. To this end, we use immunomagnetic reduction (IMR) nanobead technology to measure plasma neurofilament light chain (NfL).
The patients with IMND were enrolled in the Chang Gung Memorial Hospital at Keelung from 2018 to 2023. Seronegative patients were excluded based on the results of antibody tests. The healthy controls (HC) were community-dwelling adults from the Northeastern Taiwan Community Medicine Research Cohort (NTCMRC) conducted by the Community Medicine Research Center of the Keelung CGMH from 2020 to 2022. IMR technique detects magnetic susceptibility via measuring magnetic signal reduction caused by antigen-antibody immunocomplex formation on magnetic nanobeads. The plasma level of NfL was determined by the magnetic susceptibility changes in IMR.
The study enrolled 57 IMND patients from the hospital and 73 HC participants from the communities. The plasma NfL was significantly higher in the IMND than in the HC (11.022 ± 2.637 vs. 9.664 ± 2.610 pg/mL, p = 0.004), regardless of age effects on plasma NfL in an analysis of covariance (ANCOVA) (F = 0.720, p = 0.950). In the receiver of operation curve analysis, the area under curve for plasma NfL to discriminate IMND and HC was 0.664 (95% CI = 0.549 to 0.739, p = 0.005). The subgroup analysis of plasma NfL in the IMND patients showed no difference between peripheral immune-mediated neuropathy (IMN) and central immune-mediated encephalomyelitis (IMEM) (11.331 ± 2.895 vs. 10.627 ± 2.260 pg/mL, p = 0.322), nor between tumor and non-tumor IMND (10.784 ± 3.446 vs. 11.093 ± 2.391 pg/mL, p = 0.714). Additionally, the antibody class of ganglioside antibodies in IMN did not have an impact on plasma NfL level (p = 0.857).
Plasma NfL measurement is a reliable indicator of axonal injuries in patients with IMND. It is equally effective in detecting nerve injuries in inflammatory peripheral neuropathies and central neuroinflammation. The IMR nanobead technology offers a feasible method of detecting plasma NfL, which helps identify axonal injuries in IMND.
在免疫介导的神经疾病（IMND）中，不同的综合征与神经元表面抗原、神经元内抗原、星形胶质细胞水通道蛋白和神经节苷脂的抗体有关。这些自身抗体可能具有致病性或与神经炎症和由此产生的神经元损伤有关。本研究旨在确定一种血液生物标志物，以检测 IMND 患者的神经元损伤。为此，我们使用免疫磁减少（IMR）纳米珠技术测量血浆神经丝轻链（NfL）。
2018 年至 2023 年，我们在基隆长庚纪念医院招募了 IMND 患者。根据抗体检测结果，排除血清阴性患者。健康对照组（HC）来自基隆长庚纪念医院社区医学研究中心于 2020 年至 2022 年进行的东北台湾社区医学研究队列（NTCMRC）中的社区成年人。IMR 技术通过测量磁珠上抗原-抗体免疫复合物形成引起的磁信号减少来检测磁敏感性。通过 IMR 中磁敏感性的变化来确定血浆 NfL 的水平。
本研究共纳入 57 例来自医院的 IMND 患者和 73 例来自社区的 HC 参与者。IMND 患者的血浆 NfL 明显高于 HC（11.022±2.637 与 9.664±2.610 pg/mL，p=0.004），在协方差分析（ANCOVA）中，年龄对血浆 NfL 的影响可以忽略不计（F=0.720，p=0.950）。在受试者工作特征曲线分析中，血浆 NfL 区分 IMND 和 HC 的曲线下面积为 0.664（95%置信区间为 0.549 至 0.739，p=0.005）。IMND 患者的血浆 NfL 亚组分析显示，周围免疫介导性神经病（IMN）和中枢免疫介导性脑脊髓炎（IMEM）之间无差异（11.331±2.895 与 10.627±2.260 pg/mL，p=0.322），肿瘤与非肿瘤 IMND 之间也无差异（10.784±3.446 与 11.093±2.391 pg/mL，p=0.714）。此外，IMN 中的神经节苷脂抗体的抗体类别对血浆 NfL 水平没有影响（p=0.857）。
血浆 NfL 测量是 IMND 患者轴突损伤的可靠指标。它在检测炎症性周围神经病和中枢神经炎症中的神经损伤同样有效。IMR 纳米珠技术提供了一种可行的检测血浆 NfL 的方法，有助于识别 IMND 中的轴突损伤。
