Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the FcγRIIIa-158 V/V and V/F …

E Hatjiharissi, L Xu, DD Santos… - Blood, the Journal of …, 2007 - ashpublications.org
E Hatjiharissi, L Xu, DD Santos, ZR Hunter, BT Ciccarelli, S Verselis, M Modica, Y Cao…
Blood, the Journal of the American Society of Hematology, 2007ashpublications.org
The presence of valine (V) at position 158 of FcγRllla (CD16) is known to improve clinical
response to rituximab in indolent non-Hodgkin lymphoma (NHL). Little is known about the
basic mechanisms for this observation. We examined natural killer (NK) cells from healthy
donors representing the FcγRIIIa-158 polymorphic subgroups (V/V, V/F, and F/F) for gene
transcript and cell surface CD16 expression, rituximab binding, and rituximab-dependent NK
cell-mediated cytotoxicity. We observed higher levels of FcγRIIIa transcripts among …
The presence of valine (V) at position 158 of FcγRllla (CD16) is known to improve clinical response to rituximab in indolent non-Hodgkin lymphoma (NHL). Little is known about the basic mechanisms for this observation. We examined natural killer (NK) cells from healthy donors representing the FcγRIIIa-158 polymorphic subgroups (V/V, V/F, and F/F) for gene transcript and cell surface CD16 expression, rituximab binding, and rituximab-dependent NK cell-mediated cytotoxicity. We observed higher levels of FcγRIIIa transcripts among individuals with the FcγRIIIa-158 V/V versus V/F or F/F genotype (P < .001); increased cell surface CD16 expression by quantitative flow cytometry on NK cells from individuals expressing at least one valine at FcγRIIIa-158 versus F/F (P = .029); as well as augmented rituximab binding and rituximab-mediated, antibody-dependent cellular cytotoxicity (ADCC). These results suggest that individuals expressing at least one valine at FcγRIIIa-158 might, in part, have better clinical outcomes due to increased CD16 expression, rituximab binding, and rituximab-mediated ADCC.
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