视神经脊髓炎谱系疾病与多发性硬化患者部分脑脊液免疫标志物的比较分析

doi:10.3969/j.issn.1006-7795.2021.05.005

摘要/Abstract

摘要： 目的观察血清、脑脊液(cerebrospinal fluid,CSF)白蛋白(albumin,ALB)、免疫球蛋白、补体水平及相关合成指标在多发性硬化(multiple sclerosis,MS)和视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)中的变化,初步分析上述指标在两种疾病诊断及鉴别诊断中的意义。方法选取91例已确诊神经系统脱髓鞘患者,包括MS患者33例,NMOSD患者58例,选取头痛患者50例作为非炎性对照组。测定血清及CSF中ALB、IgA、IgM、IgG以及血清C3、C4等浓度,并计算血清免疫球蛋白与CSF免疫球蛋白比值IgA Q、IgG Q、IgM Q、ALB Q及与年龄相关的Reiber双曲线上部判别值(Reiber's upper hyperbolic discrimination line, Qlim)(ALB),计算ALB Q>Qlim (ALB)比例及IgG 24 h鞘内合成率,比较分析MS、NMOSD与头痛对照组间各指标差异。结果 MS和NMOSD组患者CSF IgG、IgG Q、IgG 24 h鞘内合成率和ALB Q>Qlim (ALB)比例均显著高于对照组(P<0.05),且MS组患者IgG 24 h鞘内合成率和IgG Q明显高于NMOSD组(P<0.05)。结论 MS和NMOSD均有血-脑脊液屏障功能损伤,而鞘内IgG的合成是MS和NMOSD的一个关键区分点,在两者的鉴别诊断中有重要意义。

关键词: 视神经脊髓炎谱系疾病, 多发性硬化, 血-脑脊液屏障, 鞘内合成

Abstract: Objective To observe the changes of several biomarkers, including ALB, immunoglobulin and complements,etc, in the serum and cerebrospinal fluid(CSF) of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), and to explore the significance of each index in the diagnosis as well as differential diagnosis of the two diseases. Methods A total of 91 patients with central nervous system demyelinating diseases were enrolled,including 33 MS patients and 58 NMOSD patients. Fifty patients with Headache (HA) were selected as non-inflammatory control group. The blood and CSF specimen were collected. ALB, IgA, IgG, IgM in the serum and CSF as well as C3, C4 in the serum were measured. The ratio of IgA, IgG, IgM,ALB in the serum and in CSF as IgA Q, IgG Q, IgM Q,ALB Q and the index of 24 h intrathecal synthesis rate and ALB Q>Qlim (ALB) were counted. The difference of the biomarkers in MS and NMOSD patients were analyzed. Results The levels of CSF IgG, IgG Q, 24 h intrathecal synthesis rate and the ratio of ALB Q>Qlim (ALB) in MS and NMOSD group were statistically significant higher than that in control group(P<0.05). Moreover, the 24 h intrathecal synthesis rate and IgG Q of MS group were significantly higher than that of NMOSD group(P<0.05). Conclusion Both MS and NMOSD featured in the impaired blood-brain barrier function, but it could be differentiated with intrathecal IgG synthesis between MS and NMOSD.

Key words: neuromyelitis optica spectrum disorders, multiple sclerosis, blood brain barrier, intrathecal synthesis

中图分类号:

R744.5

时丽丽, 王金玲, 王怡斐, 李蕾, 王培昌. 视神经脊髓炎谱系疾病与多发性硬化患者部分脑脊液免疫标志物的比较分析[J]. 首都医科大学学报, 2021, 42(5): 721-725.

Shi Lili, Wang Jinling, Wang Yifei, Li Lei, Wang Peichang. The comparative analysis of several biomarkers in the cerebrospinal fluid of multiple sclerosis and neuromyelitis optica spectrum disorders[J]. Journal of Capital Medical University, 2021, 42(5): 721-725.

参考文献

[1] Wingerchuk D M, Banwell B, Bennett J L, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2): 177-189.
[2] Kim S H, Kim W, Li X F, et al. Does interferon beta treatment exacerbate neuromyelitis optica spectrum disorder?[J]. Mult Scler, 2012, 18(10): 1480-1483.
[3] Mcdonald W I, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis[J]. Ann Neurol, 2001, 50(1): 121-127.
[4] Sellner J, Hemmer B, Muhlau M. The clinical spectrum and immunobiology of parainfectious neuromyelitis optica (Devic) syndromes[J]. J Autoimmun, 2010, 34(4): 371-379.
[5] Akaishi T, Takahashi T, Fujihara K, et al. Impact of intrathecal IgG synthesis on neurological disability in patients with multiple sclerosis[J]. Mult Scler Relat Disord, 2020, 45: 102382.
[6] Pittock S J, Lucchinetti C F. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later[J]. Ann N Y Acad Sci, 2016, 1366(1): 20-39.
[7] Hor J Y, Asgari N, Nakashima I, et al. Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide[J]. Front Neurol, 2020, 11: 501.
[8] Jarius S, Paul F, Aktas O, et al. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing[J]. J Neuroinflammation, 2018, 15(1): 134.
[9] Mcfarland H F, Martin R. Multiple sclerosis: a complicated picture of autoimmunity[J]. Nat Immunol, 2007, 8(9): 913-919.
[10]Wingerchuk D M, Lennon V A, Pittock S J, et al. Revised diagnostic criteria for neuromyelitis optica[J]. Neurology, 2006, 66(10): 1485-1489.
[11]Johanson C E, Stopa E G, Mcmillan P N. The blood-cerebrospinal fluid barrier: structure and functional significance[J]. Methods Mol Biol, 2011, 686: 101-131.
[12]曹丹丹,孙静,白云飞,等. 周细胞在慢性脑血流低灌注血-脑脊液屏障损伤中的作用[J]. 首都医科大学学报,2018, 39(4): 541-545.
[13]Reiber H. Flow rate of cerebrospinal fluid (CSF)-a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases[J]. J Neurol Sci, 1994, 122(2): 189-203.
[14]Deisenhammer F, Bartos A, Egg R, et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force[J]. Eur J Neurol, 2006, 13(9): 913-922.
[15]Akaishi T, Takahashi T, Misu T, et al. Difference in the source of anti-AQP4-IgG and anti-MOG-IgG antibodies in CSF in patients with neuromyelitis optica spectrum disorder[J]. Neurology, 2021, 97(1): e1-e12.
[16]曾敏,冯灵,李梦岚,等. 多发性硬化的临床特征及生活自理能力的影响因素观察[J]. 解放军医药杂志, 2019, 31(8): 75-78.
[17]Ontaneda D, Fox R J, Chataway J. Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives[J]. Lancet Neurol, 2015, 14(2): 208-223.
[18]Leech S, Kirk J, Plumb J, et al. Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis[J]. Neuropathol Appl Neurobiol, 2007, 33(1): 86-98.
[19]Kowarik M C, Dzieciatkowska M, Wemlinger S, et al. The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations[J]. J Neuroinflammation, 2015, 12: 19.
[20]Ciotti J R, Eby N S, Wu G F, et al. Clinical and laboratory features distinguishing MOG antibody disease from multiple sclerosis and AQP4 antibody-positive neuromyelitis optica[J]. Mult Scler Relat Disord, 2020, 45: 102399.
[21]Kowarik M C, Astling D, Gasperi C, et al. CNS Aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder[J]. Ann Clin Transl Neurol, 2017, 4(6): 369-380.
[22]Zaffaroni M, Caputo D, Cazzullo C L. Isotachophoresis evaluation of synthesis of intrathecal IgG subfractions in multiple sclerosis[J]. J Neurol, 1983, 229(1): 55-60.
[23]Gasperi V, Sibilano M, Savini I, et al. Niacin in the central nervous system: an update of biological aspects and clinical applications[J]. Int J Mol Sci, 2019, 20(4): 974.
[24]Akaishi T, Takahashi T, Fujihara K, et al. Impact of intrathecal IgG synthesis on neurological disability in patients with multiple sclerosis[J]. Mult Scler Relat Disord, 2020, 45: 102382.