Journal
NEUROLOGY
Volume 73, Issue 23, Pages 2003-2010Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3181c5b457
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Funding
- Teva Pharmaceutical Industries Ltd
- sanofi-aventis
- Bayer-Schering Pharma
- sanofiaventis
- Novartis and Biogen Idec
- Biogen Idec.
- Swedish Research Council
- European Union [LSHM-CT-2005-018637, LSHG-CT-2005-019015]
- Soderbergs Foundation
- Bibbi and Nils Jensens Foundation
- Montel Williams Foundation
- Swedish Brain Foundation
- Biogen Idec and Merck Serono
- Danish Multiple Sclerosis Society
- Biogen Idec
- Teva Pharmaceutical Industries Ltd.
- Baxter International Inc.
- BioMS Medical
- Novartis
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Background: Accumulating evidence supports a major role of B cells in multiple sclerosis (MS) pathogenesis. How B cells are recruited to the CNS is incompletely understood. Our objective was to study B-cell chemokine concentrations in MS, their relationship with disease activity, and how treatment with methylprednisolone and natalizumab affected the concentration in CSF. Methods: Using a cross-sectional design, CSF and blood samples were obtained from cohorts of patients with clinically isolated syndromes (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), or secondary progressive MS (SPMS), and noninflammatory neurologic disease control subjects. Some patients with RRMS were studied before and after treatment with methylprednisolone or natalizumab. Results: In CSF, concentrations of CXCL13, but not CXCL12, were higher in patients with CIS, RRMS, SPMS, and PPMS than in controls. CSF concentrations of CXCL13 correlated with the CSF B-cell count, with markers of immune activation, and with disease activity in patients with CIS and RRMS. CSF concentrations of CXCL13 decreased after treatment with high-dose methylprednisolone and natalizumab. High CSF concentrations of CXCL13 correlated with low expression of messenger RNA encoding the immunoregulatory cytokines interleukin 10 and transforming growth factor beta 1, but not with the expression of T-helper type 1 (Th1) and Th17 factors. Conclusion: The chemokine CXCL13 may play a major role in recruitment of B cells and T-cell subsets expressing the chemokine receptor CXCR5 to the CNS in multiple sclerosis (MS), and may be a useful biomarker for treatment effects in MS. Furthermore, CXCL13 or its receptor CXCR5 should be considered as therapeutic targets in MS. Neurology (R) 2009; 73: 2003-2010
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