Abstract
Background:
Multiple sclerosis results from T-cell-dependent inflammatory demyelination of the central nervous system. Our objective was long-term suppression of inflammation with short-term monoclonal antibody treatment.
Methods:
We depleted 95% of circulating lymphocytes in 27 patients with multiple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclonal antibody, Campath-1H. Clinical and haematological consequences of T-cell depletion, and in-vitro responses of patients' peripheral-blood mononuclear cells were analysed serially for 18 months after treatment.
Findings:
Radiological and clinical markers of disease activity were significantly decreased for at least 18 months after treatment. However, a third of patients developed antibodies against the thyrotropin receptor and carbimazole-responsive autoimmune hyperthyroidism. The depleted peripheral lymphocyte pool was reconstituted with cells that had decreased mitogen-induced proliferation and interferon gamma secretion in vitro.
Interpretation:
Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.
Publication types
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Clinical Trial
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Antigens, CD / immunology
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Antigens, Neoplasm*
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Antirheumatic Agents / administration & dosage
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Antirheumatic Agents / adverse effects*
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B-Lymphocyte Subsets / drug effects
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B-Lymphocyte Subsets / immunology
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CD4 Antigens / immunology
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CD52 Antigen
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Drug Administration Schedule
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Female
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Follow-Up Studies
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Glycoproteins / immunology
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Graves Disease / chemically induced
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Graves Disease / immunology
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Humans
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Male
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Methylprednisolone / administration & dosage
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Methylprednisolone / adverse effects
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Multiple Sclerosis, Chronic Progressive / drug therapy*
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Multiple Sclerosis, Chronic Progressive / immunology
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Pulse Therapy, Drug
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Receptors, Tumor Necrosis Factor / administration & dosage
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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Th1 Cells / drug effects
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Th1 Cells / immunology
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Thyroiditis, Autoimmune / chemically induced*
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Thyroiditis, Autoimmune / immunology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Neoplasm
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Antigens, CD
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Antigens, Neoplasm
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Antirheumatic Agents
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CD4 Antigens
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CD52 Antigen
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CD52 protein, human
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Glycoproteins
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Receptors, Tumor Necrosis Factor
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Alemtuzumab
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Methylprednisolone