Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS

F Sellebjerg; L Börnsen; M Khademi; M Krakauer; T Olsson; J L Frederiksen; P S Sørensen; F Sellebjerg; L Börnsen; M Khademi; M Krakauer; T Olsson; Jette Lautrup Battistini; Per Soelberg Sørensen

doi:10.1212/WNL.0b013e3181c5b457

Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS

F Sellebjerg, L Börnsen, M Khademi, M Krakauer, T Olsson, J L Frederiksen, P S Sørensen, F Sellebjerg, L Börnsen, M Khademi, M Krakauer, T Olsson, Jette Lautrup Battistini, Per Soelberg Sørensen

Department of Clinical Medicine

145 Citations (Scopus)

Abstract

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 beta1, 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.

Original language	English
Journal	Neurology
Volume	73
Issue number	23
Pages (from-to)	2003-10
Number of pages	7
ISSN	0028-3878
DOIs	https://doi.org/10.1212/WNL.0b013e3181c5b457 https://doi.org/10.1212/WNL.0b013e3181c5b457
Publication status	Published - 2009

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Sellebjerg, F., Börnsen, L., Khademi, M., Krakauer, M., Olsson, T., Frederiksen, J. L., Sørensen, P. S., Sellebjerg, F., Börnsen, L., Khademi, M., Krakauer, M., Olsson, T., Battistini, J. L., & Sørensen, P. S. (2009). Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology, 73(23), 2003-10. https://doi.org/10.1212/WNL.0b013e3181c5b457, https://doi.org/10.1212/WNL.0b013e3181c5b457

Sellebjerg, F, Börnsen, L, Khademi, M, Krakauer, M, Olsson, T, Frederiksen, JL, Sørensen, PS, Sellebjerg, F, Börnsen, L, Khademi, M, Krakauer, M, Olsson, T, Battistini, JL & Sørensen, PS 2009, 'Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS', Neurology, vol. 73, no. 23, pp. 2003-10. https://doi.org/10.1212/WNL.0b013e3181c5b457, https://doi.org/10.1212/WNL.0b013e3181c5b457

@article{4af17430a92b11df928f000ea68e967b,

title = "Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS",

abstract = "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 beta1, 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.",

author = "F Sellebjerg and L B{\"o}rnsen and M Khademi and M Krakauer and T Olsson and Frederiksen, {J L} and S{\o}rensen, {P S} and F Sellebjerg and L B{\"o}rnsen and M Khademi and M Krakauer and T Olsson and Battistini, {Jette Lautrup} and S{\o}rensen, {Per Soelberg}",

note = "Keywords: Adult; Aged; B-Lymphocytes; Biological Markers; Chemokine CXCL13; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Protein Transport; Receptors, CXCR5; T-Lymphocyte Subsets",

year = "2009",

doi = "10.1212/WNL.0b013e3181c5b457",

language = "English",

volume = "73",

pages = "2003--10",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "23",

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TY - JOUR

T1 - Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS

AU - Sellebjerg, F

AU - Börnsen, L

AU - Khademi, M

AU - Krakauer, M

AU - Olsson, T

AU - Frederiksen, J L

AU - Sørensen, P S

AU - Sellebjerg, F

AU - Börnsen, L

AU - Khademi, M

AU - Krakauer, M

AU - Olsson, T

AU - Battistini, Jette Lautrup

AU - Sørensen, Per Soelberg

N1 - Keywords: Adult; Aged; B-Lymphocytes; Biological Markers; Chemokine CXCL13; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Protein Transport; Receptors, CXCR5; T-Lymphocyte Subsets

PY - 2009

Y1 - 2009

N2 - 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 beta1, 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.

AB - 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 beta1, 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.

U2 - 10.1212/WNL.0b013e3181c5b457

DO - 10.1212/WNL.0b013e3181c5b457

M3 - Journal article

C2 - 19996075

SN - 0028-3878

VL - 73

SP - 2003

EP - 2010

JO - Neurology

JF - Neurology

IS - 23

ER -

Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS

Abstract

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