Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis

  • Lars Börnsen
    University of Copenhagen and Danish MS Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
  • Mohsen Khademi
    Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
  • Tomas Olsson
    Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
  • Per Soelberg Sørensen
    University of Copenhagen and Danish MS Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
  • Finn Sellebjerg
    University of Copenhagen and Danish MS Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

説明

<jats:p>Background:The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity.</jats:p><jats:p>Objective:The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS.</jats:p><jats:p>Methods:Our research consisted of a cross-sectional study of patients from two randomized, placebo-controlled trials. Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay (ELISA). Samples were obtained from untreated patients with exacerbation of clinically isolated syndrome (CIS) ( n = 25) and relapsing–remitting MS (RRMS) ( n = 41) of whom 48 participated in clinical trials, randomly allocated to treatment with placebo or methylprednisolone (MP) and undergoing repeated sampling after 3 weeks. Furthermore, we obtained CSF and blood samples from patients with primary progressive MS (PPMS, n = 9), secondary progressive MS (SPMS, n = 28) and other neurological disorders (OND, n = 44), and blood samples from 24 healthy subjects.</jats:p><jats:p>Results:OPN concentrations were significantly increased in the CSF of patients with CIS ( p = 0.02) and RRMS ( p < 0.001) in exacerbation compared to patients with OND, and increased levels of OPN were associated with high values of other biomarkers of inflammation. At 3-week follow-up CSF OPN concentrations had decreased significantly from baseline regardless treatment with placebo or MP. Patients with PPMS had increased OPN levels in the CSF ( p = 0.004) and high CSF levels of OPN were associated with high degrees of disability.</jats:p><jats:p>Conclusions:OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS, presumably reflecting ongoing inflammation. Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients.</jats:p>

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