Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis
Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis
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DOI：
10.1177/1352458514561906
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发表时间：
2015-09-01
影响因子：
5.8
通讯作者：
Thouvenot, E.
中科院分区：
文献类型：
--
作者：
Hinsinger, G.;Galeotti, N.;Thouvenot, E.
背景：尽管MRI诊断多发性硬化症（MS）的敏感性，预后生物标志物仍然需要优化治疗。目的：利用定量蛋白质组学技术鉴定多发性硬化症脑脊液诊断标志物，并分析其在不同疾病阶段的表达。方法：我们对对照组和复发缓解型多发性硬化（RRMS）患者的脑脊液蛋白质组进行了差异分析，然后用ELISA法验证了对照组、临床孤立综合征（CIS）、RRMS和进展型多发性硬化（PMS）患者脑脊液和血清中的候选生物标志物。结果：527个定量蛋白中有22个在对照和RRMS CSF中表现出不同的丰度。其中包括几丁质酶3样蛋白1 （CHI3L1）和2 (CHI3L2)，它们在MS患者的大脑中表达强烈，特别是在来自白质斑块的星形胶质细胞和小胶质细胞中。脑脊液和血清CHI3L1水平随疾病分期升高而升高，脑脊液（>189 ng/ml）和血清（>33 ng/ml）高的CIS患者CHI3L1转化为RRMS的速度更快（log rank检验，p < 0.05和p < 0.001）。相比之下，PMS患者的脑脊液CHI3L2水平低于RRMS患者。因此，CSF CHI3L1/CHI3L2比值能准确区分PMS和RRMS。结论：脑脊液CHI3L1、CHI3L2和血清CHI3L1可能有助于确定多发性硬化症的分期，对CIS患者有预后价值。
Background: Despite sensitivity of MRI to diagnose multiple sclerosis (MS), prognostic biomarkers are still needed for optimized treatment.Objective: The objective of this paper is to identify cerebrospinal fluid (CSF) diagnostic biomarkers of MS using quantitative proteomics and to analyze their expression at different disease stages.Methods: We conducted differential analysis of the CSF proteome from control and relapsing-remitting MS (RRMS) patients followed by verification by ELISA of candidate biomarkers in CSF and serum in control, clinically isolated syndrome (CIS), RRMS and progressive MS (PMS) patients.Results: Twenty-two of the 527 quantified proteins exhibited different abundances in control and RRMS CSF. These include chitinase 3-like protein 1 (CHI3L1) and 2 (CHI3L2), which showed a strong expression in brain of MS patients, especially in astrocytes and microglial cells from white matter plaques. CSF and serum CHI3L1 levels increased with the disease stage and CIS patients with high CSF (>189 ng/ml) and serum (>33 ng/ml) CHI3L1 converted more rapidly to RRMS (log rank test, p < 0.05 and p < 0.001, respectively). In contrast, CSF CHI3L2 levels were lower in PMS than in RRMS patients. Accordingly, CSF CHI3L1/CHI3L2 ratio accurately discriminated PMS from RRMS.Conclusions: CSF CHI3L1 and CHI3L2 and serum CHI3L1 might help to define MS disease stage and have a prognostic value in CIS.