神经丝蛋白轻链与多发性硬化的相关性研究

Neurofilament protein light in multiple sclerosis

目的研究轴索损伤标志物神经丝蛋白轻链(NF-L)及其抗体检测对多发性硬化(MS)诊断及预后的意义,并进一步揭示 MS 的发病机制。方法以酶联免疫吸附实验(ELISA)方法检测了63例 MS 患者、15例视神经脊髓炎(ONM)及其他各对照组[31例其他神经系统炎性疾病(OIND)、18例其他非炎性神经系统疾病(NIND)以及46名神经系统正常对照(NC)]血清和脑脊液中 NF-L 及其抗体、抗髓鞘碱性蛋白(MBP)、抗髓鞘少突胶质细胞糖蛋白(MOG)抗体水平。正态分布资料用x^-±s表示,非正态分布资料用 M(QR)表示。结果脑脊液中 NF-L 浓度 MS 组为26(33)ng/L,ONM组为20(92)ng/L,OIND 组为19(82)ng/L,NIND 组为30(194)ng/L,NC 组为10(7)ng/L。其他各组脑脊液中 NF-L 浓度与 NC 组相比均明显增高(均 P<0.01);NF-L 抗体水平 MS 组低于 OIND 组,高于 NIND 组及 NC 组(均 P<0.05)。MS 患者脑脊液中 NF-L 抗体水平与 MBP 抗体水平(r=0.784,P<0.01)和 IgG 水平(r=0.675,P<0.01)显著相关;但与 MOG 抗体水平无相关性。结论 NF-L 或其抗体测定不能作为鉴别各种神经系统疾病的理想标志物;MS、ONM、OIND、NIND 各组中均存在轴索损伤;炎症可能并非是 NF-L 抗体产生从而导致轴索损伤的主要原因。

Objective To determine if neurofilament protein light （NF-L） and anti-NF-L antibody can be used as biologic markers in diagnosing multiple sclerosis （MS） and assessing prognosis thereof. Methods Samples of cerebrospinal fluid （CSF） and serum were corrected from 63 MS patients, 15 patients with neuromyelitis optica （ONM）, 31 patients with other inflammatory neurological disease （OIND）, 18 patients with noninflammatory neurological disease （NIND）, and 46 neurological normal controls （NC group）, all age- and sex- matched. ELISA was used to detect the concentrations of NF-L, anti-NF-L antibody, anti-myelin basic protein （MBP） antibody, and anti-myelin oligo-dendroglia glycoprotein （MOG） antibody in serum and cerebral spinal fluid. And the IgG level was tested. Results The CSF levels of NF-L of the MS, ONM, OIND, and NIND groups were 26 ng/L （33） , 20 ng/L （92）, 19 ng/ L （82） , and 30 ng/L （194） respectively, without significant differences among these different groups, but all significantly higher than that of the NC group （ 10 ng/L, all P 〈 0. 01 ）. No NF-L was detected in the serum specimens of all groups. The CSF NF-L antibody level of the MS group was significantly lower than that of the OIND group （P 〈 0. 01 ）, and significantly higher than those of the NIND and NC groups （both P 〈 0. 05 ）. The CSF anti-NF-L antibody level of the MS patients was positively correlated with the MBP antibody level （r=0.784,P〈0.01） and the IgG level （r=0. 675,P〈0.01）. Conclusion Neither the NF-L nor the anti-NF-L antibody can be used as reliable biological markers for the diagnosis of MS. Strongly increased levels of NF-L were observed in patients with MS, ONM, OIND, and NIND, suggesting the occurrence of axonal injury in these conditions. Inflammation may not lead to the generation of anti-NF-L antibody which links to the axonal injury.