Increased Osteopontin Levels in the Cerebrospinal Fluid of Patients With Multiple Sclerosis

Abstract

Objective: To determine cerebrospinal fluid levels of osteopontin (OPN), a proinflammatory cytokine that was found to be overexpressed in multiple sclerosis lesions and increased in plasma during relapses and in secondary progressive multiple sclerosis. Design: Case series. Osteopontin, interleukin 12p40 (IL-12p40), IL-10, and matrix metalloproteinase 9 were measured by enzyme-linked immunosorbent assay by an investigator unaware of the patients' diagnoses. Patients: Consecutive patients with multiple sclerosis (n = 27), or other inflammatory (n = 11) or noninflammatory (n = 23) neurological diseases, undergoing lumbar puncture, were investigated. Results: Osteopontin was significantly elevated in the cerebrospinal fluid of patients with multiple sclerosis (mean [SD], 415 [186] ng/mL) and other inflammatory diseases (563 [411] ng/mL) compared with those with noninflammatory neurological diseases (286 [150] ng/ mL). Cerebrospinal fluid OPN levels were slightly higher than plasma OPN levels. Cerebrospinal fluid OPN levels positively correlated with the ability to detect cerebrospinal fluid IL-12p40. Conclusion: Osteopontin in the cerebrospinal fluid may be, in part, of central nervous system origin, and may play an important role in central nervous system inflammation.

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement

“…This observation stays in agreement with numerous other studies reporting elevated OPN levels in CSF and/or peripheral blood of MS patients as compared to healthy controls, and non-inflammatory neurological diseases [23]. Noteworthily, in our study the CSF concentration of OPN was similar in patients with MS and SID, which supports earlier findings in other groups of various SID patients [21,22]. However, there are also reports with contradictory findings, which may result from a variety of reasons, including different diseases classified as inflammatory CNS conditions in particular studies, differences of age and comorbidity structure [23,46].…”

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement

“…This observation stays in agreement with numerous other studies reporting elevated OPN levels in CSF and/or peripheral blood of MS patients as compared to healthy controls, and non-inflammatory neurological diseases [23]. Noteworthily, in our study the CSF concentration of OPN was similar in patients with MS and SID, which supports earlier findings in other groups of various SID patients [21,22]. However, there are also reports with contradictory findings, which may result from a variety of reasons, including different diseases classified as inflammatory CNS conditions in particular studies, differences of age and comorbidity structure [23,46].…”

The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment‐sensitive biomarkers

“…The increased OPN concentration that we found in CSF baseline samples from RRMS patients is in accordance with recently published data on OPN levels in the CSF in MS [35]. Hereby the enhanced OPN concentrations in CSF presumably reflect MS-related inflammation, as OPN is an inducer of the pro-inflammatory immunity [14,15] and in inflammatory neurological diseases other than MS OPN concentrations are also significantly increased [35]. We found detectable levels of MMP-9 only in baseline samples from some RRMS patients.…”

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

“…High levels of OPN have been found in plasma of RRMS patients, with greater concentrations in patients with active disease compared with those without exacerbations [100][101][102][103] and during relapses compared with remissions [102,104,105] . Similar results were found in other studies [96,101,106] , with significantly higher CSF and serum OPN levels in MS patients compared with controls [102,[107][108][109][110] . A positive correlation between IL-17 and both OPN and IL-23 concentrations has also been found [106] .…”

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement

“…This observation stays in agreement with numerous other studies reporting elevated OPN levels in CSF and/or peripheral blood of MS patients as compared to healthy controls, and non-inflammatory neurological diseases [23]. Noteworthily, in our study the CSF concentration of OPN was similar in patients with MS and SID, which supports earlier findings in other groups of various SID patients [21,22]. However, there are also reports with contradictory findings, which may result from a variety of reasons, including different diseases classified as inflammatory CNS conditions in particular studies, differences of age and comorbidity structure [23,46].…”

The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment‐sensitive biomarkers

“…The increased OPN concentration that we found in CSF baseline samples from RRMS patients is in accordance with recently published data on OPN levels in the CSF in MS [35]. Hereby the enhanced OPN concentrations in CSF presumably reflect MS-related inflammation, as OPN is an inducer of the pro-inflammatory immunity [14,15] and in inflammatory neurological diseases other than MS OPN concentrations are also significantly increased [35]. We found detectable levels of MMP-9 only in baseline samples from some RRMS patients.…”

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

“…High levels of OPN have been found in plasma of RRMS patients, with greater concentrations in patients with active disease compared with those without exacerbations [100][101][102][103] and during relapses compared with remissions [102,104,105] . Similar results were found in other studies [96,101,106] , with significantly higher CSF and serum OPN levels in MS patients compared with controls [102,[107][108][109][110] . A positive correlation between IL-17 and both OPN and IL-23 concentrations has also been found [106] .…”

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement

“…This observation stays in agreement with numerous other studies reporting elevated OPN levels in CSF and/or peripheral blood of MS patients as compared to healthy controls, and non-inflammatory neurological diseases [23]. Noteworthily, in our study the CSF concentration of OPN was similar in patients with MS and SID, which supports earlier findings in other groups of various SID patients [21,22]. However, there are also reports with contradictory findings, which may result from a variety of reasons, including different diseases classified as inflammatory CNS conditions in particular studies, differences of age and comorbidity structure [23,46].…”

The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment‐sensitive biomarkers

“…The increased OPN concentration that we found in CSF baseline samples from RRMS patients is in accordance with recently published data on OPN levels in the CSF in MS [35]. Hereby the enhanced OPN concentrations in CSF presumably reflect MS-related inflammation, as OPN is an inducer of the pro-inflammatory immunity [14,15] and in inflammatory neurological diseases other than MS OPN concentrations are also significantly increased [35]. We found detectable levels of MMP-9 only in baseline samples from some RRMS patients.…”

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

“…High levels of OPN have been found in plasma of RRMS patients, with greater concentrations in patients with active disease compared with those without exacerbations [100][101][102][103] and during relapses compared with remissions [102,104,105] . Similar results were found in other studies [96,101,106] , with significantly higher CSF and serum OPN levels in MS patients compared with controls [102,[107][108][109][110] . A positive correlation between IL-17 and both OPN and IL-23 concentrations has also been found [106] .…”