González-Jiménez Adela, Urcelay Elena, Espino-Paisán Laura
Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clinico San Carlos (IdISSC), Madrid, Spain.
Cooperative Research Networks Oriented to Health Results (RICORS, REI), Health Research Institute Carlos III (ISCIII), Madrid, Spain.
Front Immunol. 2025 Jun 16;16:1597117. doi: 10.3389/fimmu.2025.1597117. eCollection 2025.
Multiple sclerosis (MS) is a neuroinflammatory complex disease of the central nervous system (CNS). Diagnosing MS remains challenging due to its nonspecific signs, highlighting the need for reliable biomarkers. One potential biomarker is osteopontin (OPN), found in cerebrospinal fluid (CSF) and peripheral blood. This article presents a systematic review and meta-analysis of the association between OPN levels in CSF and blood and the presence of MS.
We searched PubMed, Embase, and Cochrane databases for articles measuring OPN concentrations in peripheral blood and CSF samples from MS patients, published before July 12, 2024. A total of 605 articles were identified, and 29 were included in the analysis. Risk of bias was assessed with the NOS scale. The study protocol was officially registered in the PROSPERO website (registration number: CRD42023473406). We extracted standardized mean differences, 95% confidence intervals, and two-sided p values from each study and conducted a meta-analysis using a random-effects model. The heterogeneity among studies was evaluated by I-squared (I2), with values greater than 40% indicating high heterogeneity.
The present analysis revealed that individuals who suffered a first episode suggestive of MS, Clinically Isolated Syndrome (CIS), exhibited higher OPN levels in CSF than controls and patients with other neurological disorders (OND), emerging as an additional diagnosis tool. Furthermore, the observed decrease of OPN levels after Natalizumab (NTZ) treatment evidenced its potential as a biomarker of its efficacy. Higher OPN levels were found in CSF of individuals with MS compared to healthy controls (HC) and subjects with no other neurological diseases (NOND), result corroborated in relapsing remitting (RRMS) and secondary progressive (SPMS) patients. Similar OPN levels were observed when comparing MS patients to OND patients, suggesting that elevated OPN levels may be a common feature across various neurological conditions.
https://www.crd.york.ac.uk/prospero/, identifier CRD42023473406.
多发性硬化症（MS）是一种中枢神经系统（CNS）的神经炎症性复杂疾病。由于其体征不具有特异性，MS的诊断仍然具有挑战性，这凸显了对可靠生物标志物的需求。一种潜在的生物标志物是骨桥蛋白（OPN），它存在于脑脊液（CSF）和外周血中。本文对脑脊液和血液中OPN水平与MS存在之间的关联进行了系统综述和荟萃分析。
我们在PubMed、Embase和Cochrane数据库中搜索了2024年7月12日前发表的测量MS患者外周血和脑脊液样本中OPN浓度的文章。共识别出605篇文章，其中29篇纳入分析。采用NOS量表评估偏倚风险。该研究方案已在PROSPERO网站正式注册（注册号：CRD42023473406）。我们从每项研究中提取标准化均数差、95%置信区间和双侧p值，并使用随机效应模型进行荟萃分析。采用I²评估研究间的异质性，I²值大于40%表示高度异质性。
本分析显示，患有首次提示MS的临床孤立综合征（CIS）的个体，其脑脊液中的OPN水平高于对照组和其他神经系统疾病（OND）患者，这使其成为一种额外的诊断工具。此外，那他珠单抗（NTZ）治疗后观察到的OPN水平下降证明了其作为疗效生物标志物的潜力。与健康对照（HC）和无其他神经系统疾病（NOND）的受试者相比，MS患者脑脊液中的OPN水平更高，复发缓解型（RRMS）和继发进展型（SPMS）患者也得到了类似结果。将MS患者与OND患者进行比较时观察到类似的OPN水平，这表明OPN水平升高可能是各种神经系统疾病的共同特征。
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