Abstract
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity involving FcγRIIIa (CD16) likely contributes to the clinical efficacy of rituximab. To assess the in vivo effects of CD16 polymorphisms on rituximab-induced NK activation, blood was evaluated before and 4 hours after initiation of the initial dose of rituximab in 21 lymphoma subjects. Rituximab induced NK activation and a drop in circulating NK-cell percentage in subjects with the high-affinity [158(VF/VV)] but not the low-affinity [158(FF)] CD16 polymorphism. There was no correlation between NK-cell activation or NK-cell percentage and polymorphisms in CD32A, C1q, or CH50. We conclude that NK activation occurs within 4 hours of rituximab infusion in subjects with the high-affinity CD16 polymorphism but not those with the low-affinity CD16 polymorphism. This finding may help explain the superior clinical outcome seen in the subset of high-affinity CD16 polymorphism lymphoma patients treated with single-agent rituximab.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antibodies, Monoclonal, Murine-Derived / administration & dosage
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Antibodies, Monoclonal, Murine-Derived / therapeutic use*
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Antibody Affinity
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Antibody-Dependent Cell Cytotoxicity / drug effects*
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Antibody-Dependent Cell Cytotoxicity / immunology
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / therapeutic use
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Female
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GPI-Linked Proteins / immunology
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GPI-Linked Proteins / metabolism
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Humans
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Immunologic Factors / administration & dosage
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Immunologic Factors / therapeutic use
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Infusions, Intravenous
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Killer Cells, Natural / cytology
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Killer Cells, Natural / drug effects*
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Killer Cells, Natural / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Lymphoma* / drug therapy
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Lymphoma* / immunology
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Lymphoma* / pathology
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Male
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Middle Aged
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Polymorphism, Genetic / immunology
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Protein Binding
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Receptors, IgG / immunology
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Receptors, IgG / metabolism*
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Rituximab
Substances
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents
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FCGR3B protein, human
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GPI-Linked Proteins
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Immunologic Factors
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Receptors, IgG
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Rituximab