Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism

Blood. 2011 Sep 22;118(12):3347-9. doi: 10.1182/blood-2011-05-351411. Epub 2011 Jul 18.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antibody Affinity
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Female
  • GPI-Linked Proteins / immunology
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use
  • Infusions, Intravenous
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphoma* / drug therapy
  • Lymphoma* / immunology
  • Lymphoma* / pathology
  • Male
  • Middle Aged
  • Polymorphism, Genetic / immunology
  • Protein Binding
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism*
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Immunologic Factors
  • Receptors, IgG
  • Rituximab