脑脊液 | 多种疾病的标志物

整理部分文献，根据疾病记录下文章中报道的相关标志物。

01 神经精神性红斑狼疮(NPSLE)

neuropsychiatric systemic lupus erythematosus（NPSLE）的serum和CSF标志物的荟萃分析[1]。

There was a significantly greater proportion of NPSLE patients who demonstrated positivity for serum anti-cardiolipin (aCL) Abs (OR = 1.63, p = 0.016), lupus anticoagulants (LA) Abs (OR = 1.91 p = 0.01), anti-phospholipid (APL) Abs (OR = 2.08, p = 0.001), anti-ribosomal P Abs (OR = 2.29, p < 0.001), anti-neuronal Abs (OR = 9.50, p < 0.001) as compared to SLE patients. In NPSLE patients, there was a significant increased prevalence of positive titres for CSF anti-neuronal Abs (OR = 36.84, p = 0.001) as compared to SLE patients.

02 脑炎

• 区分感染性脑炎和自身免疫脑炎：CSF细胞因子/趋化因子 [2]

A combination panel of cytokine/chemokines consisting of CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10
measured using multiplex immunoassay may be used to diagnose and monitor intrathecal inflammation in the brain. Given their association with worse outcome, certain key chemokines (CXCL13, CXCL10) could represent potential therapeutic targets in encephalitis.

• 儿童脑炎的诊断及管理 [3]
  病因确定之CSF分析：
  病毒鉴定——PCR
  生化——葡萄糖、乳酸盐，寡克隆区带（oligoclonal bands）
  其他——单核细胞增多(pleocytosis)，蛋白水平，红细胞计数

03 神经炎性中枢神经系统疾病

综述了神经炎性中枢神经系统疾病的 CSF细胞因子/趋化因子标志物，文章纳入了83篇文献 [4]。

B细胞的标志物，如CXCL13和BAFF在自身抗体相关疾病中较高；
干扰素γ(IFN-γ)在病毒性脑炎中较高；
细胞因子Th2 和 Th17在急性播散性脑脊髓炎(ADEM)和神经脊髓炎(NMO)中较高；
细胞因子Th1 和 Th17在多发性硬化 (MS)中较高。

04 精神类疾病

荟萃分析比较精神分裂症(SCZ)、双相情感障碍(BP)、重度抑郁症(MDD)之间的CSF细胞因子和色氨酸分解代谢物的差异 [5]。文章共纳入了28篇研究文献，与健康对照比较：
IL-1β和犬尿酸的CSF水平在SCZ和BP患者中显著更高；
IL-6 和 IL-8 的CSF水平在SCZ和MDD患者中显著更高。

05 多发性硬化症

multiple sclerosis (MS)
作者回顾了脑脊液动力学的生理病理基础，以及脑脊液常规分析和MS脑脊液生物标志物的最新进展 [6]。

强调CSF的oligoclonal IgG bands (OCB)在MS诊断和预后中的作用及重要性;
**Free light chains (FLC) **：Ig由轻链和重链组成，由于轻链本身比重链产生的多，因此在血清、尿液和CSF等中都可以检测到FLC。病理状态下，Ig升高的同时也会伴随FLC的升高，这在MS中多次被报道。因此可以将CSF的FLC作为辅助诊断MS的标志物 (也属于检测OCB）；
oligoclonal IgM bands：MS预后，待进一步研究。

新的标志物（待进一步研究确认）：**CXCL13、Neurofilaments (Nf)、IgG galactosylation、Chitinase 3 like 1 (CHI3L1)、Micro-RNAs (miRNAs,miR-326, miR-92a, miR-922, miR-181c, and miR-633...) **

关于OCB：

OCB的概念

配对检测

06 脑部肿瘤

针对89例样本（18例非肿瘤 vs. 不同类型肿瘤）的CSF进行small RNAseq [7]。

MiR-10a-5p and miR-196a-5p have significantly highest levels in CSF of GBM samples. Moreover, 6 miRNAs (miR-30c-5p, miR-30e-5p, miR-145-5p, miR-320c, miR-3960, and miR-6131) indicated significantly different levels between GBM and LGG (P<0.01).

07 偏头痛

偏头痛的荟萃分析，纳入了40项研究 [8]。
Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

参考资料：

1. Ho, R. C., Thiaghu, C., Ong, H. Y., Lu, Y. X., Ho, C. S., Tam, W. W., & Zhang, M. W. (2016). A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmunity Reviews, 15(2), 124-138. doi: 10.1016/j.autrev.2015.10.003
2. Kothur K, Wienholt L, Mohammad SS, Tantsis EM, Pillai S, Britton PN, et al. (2016) Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis. PLoS ONE 11(8): e0161656.
3. Clara Thompson, Rachel Kneen, Andrew Riordan, Dominic Kelly, Andrew J Pollard. Encephalitis in children. Arch Arch Dis Child 2012;97:150–161
4. Kothur K, Wienholt L, Brilot F, et al. CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review[J]. Cytokine, 2016, 77: 227-237.
5. Alexandre K Wang, Brian J Miller; Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression, Schizophrenia Bulletin, Volume 44, Issue 1, 13 January 2018, Pages 75–83, https://doi.org/10.1093/schbul/sbx035
6. Matteo Gastaldi, Elisabetta Zardini & Diego Franciotta (2017) An update on the use of cerebrospinal fluid analysis as a diagnostic tool in multiple sclerosis,Expert Review of Molecular Diagnostics, 17:1, 31-46, DOI: 10.1080/14737159.2017.1262260
7. Analysis of microRNAs in cerebrospinal fluid of brain tumor patients
8. van Dongen R M, Zielman R, Noga M, et al. Migraine biomarkers in cerebrospinal fluid: a systematic review and meta-analysis[J]. Cephalalgia, 2017, 37(1): 49-63.