Abstract
Introduction:
Treatment with alemtuzumab is highly effective in relapsing-remitting multiple sclerosis; however, 30% of patients develop autoimmunity. Alemtuzumab (previously called Campath 1-H) induces a prolonged T-cell lymphopenia with memory cells dominating the reconstituting T-cell pool for at least 3 months.
Results:
Here we show that B-cell recovery is rapid, returning to baseline by 3 months and rising to 165% of baseline by 12 months after treatment. Immature transitional 1 B cells are the predominant cell type 1 month after treatment. This coincides with a surge in serum B-cell activating factor (BAFF), which remains elevated by 33% for at least 12 months after alemtuzumab. BAFF is critical for transition to the mature naive B-cell phenotype, which dominates from 3 months after alemtuzumab. Differentiation to memory B cells is slow so there are radical and prolonged alterations to the B-cell pool after alemtuzumab.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Alemtuzumab
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm / administration & dosage*
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Antibodies, Neoplasm / adverse effects
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B-Cell Activating Factor / biosynthesis*
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B-Cell Activating Factor / blood
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B-Cell Activating Factor / genetics
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B-Lymphocytes / drug effects*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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B-Lymphocytes / pathology
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Cell Differentiation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Female
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Follow-Up Studies
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Humans
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Immunologic Memory / drug effects
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Immunophenotyping
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Male
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Middle Aged
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Multiple Sclerosis, Relapsing-Remitting / blood
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Multiple Sclerosis, Relapsing-Remitting / drug therapy*
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Multiple Sclerosis, Relapsing-Remitting / immunology
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Multiple Sclerosis, Relapsing-Remitting / pathology
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm
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B-Cell Activating Factor
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TNFSF13B protein, human
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Alemtuzumab