PubMed:20558389
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/20558389","sourcedb":"PubMed","sourceid":"20558389","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/20558389","text":"Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis.\nBACKGROUND: 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.\nOBJECTIVE: 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.\nDESIGN: Phase 2 trial of rituximab as an add-on therapy.\nSETTING: 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)).\nMAIN 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.\nRESULTS: 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.\nCONCLUSIONS: 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.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_20558389_5_0","span":{"begin":391,"end":410},"obj":"expanded"},{"id":"SS2_20558389_5_0","span":{"begin":412,"end":415},"obj":"abbr"}],"relations":[{"id":"AE1_20558389_5_0","pred":"abbreviatedTo","subj":"SS1_20558389_5_0","obj":"SS2_20558389_5_0"}],"attributes":[{"subj":"SS1_20558389_5_0","pred":"source","obj":"Allie"},{"subj":"SS2_20558389_5_0","pred":"source","obj":"Allie"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#93ecb4","default":true}]}]}}