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Meta-Analysis
. 2025 Jun 16:16:1597117.
doi: 10.3389/fimmu.2025.1597117. eCollection 2025.

Osteopontin as a diagnostic and NTZ-response biomarker of multiple sclerosis: a systematic review and meta-analysis

Adela González-Jiménez  1   2 , Elena Urcelay  1   2 , Laura Espino-Paisán  1   2
Affiliations
Meta-Analysis

Osteopontin as a diagnostic and NTZ-response biomarker of multiple sclerosis: a systematic review and meta-analysis

Adela González-Jiménez et al. Front Immunol. .

Abstract

Introduction: 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.

Methods: 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.

Results and discussion: 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.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023473406.

Keywords: diagnostic biomarker; multiple sclerosis; natalizumab; osteopontin; treatment response.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Meta-analysis of OPN levels in MS compared to controls: (A) MS patients versus OND in CSF. (B) MS patients versus OND in plasma. (C) MS patients versus HC and NOND in CSF. (D) MS patients versus HC and NOND in plasma.
Figure 2
Figure 2
Meta-analysis of OPN levels in RRMS compared to controls: (A) RRMS patients versus OND in CSF. (B) RRMS patients versus OND in plasma. (C) RRMS patients versus HC and NOND in CSF. (D) RRMS patients versus HC and NOND in serum. (E) RRMS patients versus HC and NOND in plasma.
Figure 3
Figure 3
Meta-analysis of OPN levels in PPMS compared to controls: (A) PPMS patients versus OND in CSF. (B) PPMS patients versus HC and NOND in CSF. (C) PPMS patients versus HC and NOND in plasma.
Figure 4
Figure 4
Meta-analysis of OPN levels in SPMS compared to controls: (A) SPMS patients versus OND in CSF. (B) SPMS patients versus OND in plasma. (C) SPMS patients versus HC and NOND in CSF. (D) SPMS patients versus HC and NOND in plasma.
Figure 5
Figure 5
Meta-analysis of OPN levels in CIS compared to controls: (A) CIS patients versus OND in CSF. (B) CIS patients versus HC and NOND in CSF. (C) CIS patients versus HC and NOND in serum.
Figure 6
Figure 6
Meta-analysis of OPN levels in RRMS compared to progressive clinical forms: (A) RRMS patients versus PPMS patients in CSF. (B) RRMS patients versus PPMS patients in plasma. (C) RRMS patients versus PPMS patients in serum. (D) RRMS patients versus SPMS patients in CSF. (E) RRMS patients versus SPMS patients in plasma.
Figure 7
Figure 7
Meta-analysis of OPN levels between progressive clinical forms: (A) PPMS patients versus SPMS patients in CSF. (B) PPMS patients versus SPMS patients in plasma.
Figure 8
Figure 8
Meta-analysis of OPN levels in CIS compared to RRMS and progressive clinical forms: (A) CIS patients versus RRMS patients in CSF. (B) CIS patients versus RRMS patients in serum. (C) CIS patients versus PPMS patients in CSF. (D) CIS patients versus PPMS patients in plasma. (E) CIS patients versus PPMS patients in serum. (F) CIS patients versus SPMS patients in CSF. (G) CIS patients versus SPMS patients in plasma.
Figure 9
Figure 9
Meta-analysis of OPN levels in NTZ treatment. (A) MS before NTZ treatment versus HC in plasma. (B) MS patients treated with NTZ versus HC patients in plasma. (C) MS patients before and after NTZ treatment in plasma.
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