title: Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism.
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.
authors.affiliation: Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Veeramani
authors.forename: Siao-Yi
authors.initials: SY
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Dahle
authors.forename: Sue
authors.initials: S
authors.lastname: Blackwell
authors.forename: Laura
authors.initials: L
authors.lastname: Jacobus
authors.forename: Tina
authors.initials: T
authors.lastname: Knutson
authors.forename: Anna
authors.initials: A
authors.lastname: Button
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000915:Antibody Affinity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000276:immunology; D011485:Protein Binding; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D017452:Receptors, IgG; D000069283:Rituximab