Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis.
Arch Neurol
; 67(6): 707-14, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20558389
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 OUTCOMEMEASURES:
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Linfócitos T
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Citocinas
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Fatores Imunológicos
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Anticorpos Monoclonais
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Esclerose Múltipla
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article