期刊
MULTIPLE SCLEROSIS JOURNAL
卷 17, 期 1, 页码 32-42出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458510382247
关键词
Biomarker; CSF; immunology; multiple sclerosis; osteopontin
资金
- Danish Multiple Sclerosis Society
- Warwara Larsen Foundation
- Johnsen Memorial Foundation
- Lily Benthine Lund Foundation
- Novo Nordisk Foundation
- Danish Medical Research Council, Brdr Ronje Holding
- Ludvig & Sara Elsass Foundation
- Toyota Foundation
- Swedish Research Council
- Montel Williams Foundation
- Bibbi and Niels Jensens Foundation [LSHM-CT-2005-018637]
- Biogen Idec
Background: The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity. Objective: The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS. 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. 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. 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.
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