Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS.
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.


CONCLUSIONS
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.
Sellebjerg
F
F
University of Copenhagen and Danish MS Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. sellebjerg@dadlnet.dk
Börnsen
L
L
Khademi
M
M
Krakauer
M
M
Olsson
T
T
Frederiksen
J L
JL
Sørensen
P S
PS
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D054382:Chemokine CXCL13 / Q000097:blood / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000145:classification / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D054380:Receptors, CXCR5 / Q000096:biosynthesis / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D054380:Receptors, CXCR5