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Arch Neurol. 2010 Jun;67(6):707-14. doi: 10.1001/archneurol.2010.99.

Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis.

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  • 1Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

Abstract

BACKGROUND:

B cells are implicated in the pathogenesis of multiple sclerosis. A beneficial effect of B-cell depletion using rituximab has been shown, but the complete mechanism of action for this drug is unclear.

OBJECTIVE:

To determine the relationship between T and B cells and changes in cerebrospinal fluid (CSF) chemokine levels with rituximab, a monoclonal antibody that targets CD20.

DESIGN:

Phase 2 trial of rituximab as an add-on therapy.

SETTING:

The John L. Trotter Multiple Sclerosis Center, Washington University. Participants and Intervention Thirty subjects who had relapsing-remitting multiple sclerosis with clinical and magnetic resonance imaging activity despite treatment with an immunomodulatory drug received 4 weekly doses of rituximab (375 mg/m(2)).

MAIN OUTCOME MEASURES:

Lumbar puncture was performed before and after rituximab infusions in 26 subjects. Levels of B and T lymphocytes in the CSF were enumerated by flow cytometry, and chemoattractant levels were measured by enzyme-linked immunosorbent assay.

RESULTS:

After rituximab administration, CSF B-cell levels were decreased or undetectable in all subjects, and CSF T-cell levels were reduced in 21 subjects (81%). The mean reduction in CSF cellularity was 95% for B cells and 50% for T cells. After rituximab infusion, CSF CXCL13 and CCL19 levels decreased (P = .002 and P = .03, respectively). The proportional decline in CSF T-cell levels correlated with the proportional decrease in CXCL13 levels (r = 0.45; P = .03), suggesting a possible relationship. The CSF IgG index, IgG concentration, and oligoclonal band number were unchanged following treatment.

CONCLUSIONS:

In subjects with multiple sclerosis, B cells are critical for T-cell trafficking into the central nervous system and may alter the process by influencing chemokine production within the central nervous system.

PMID:
20558389
[PubMed - indexed for MEDLINE]
PMCID:
PMC2918395
Free PMC Article
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