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

The presence of valine (V) at FcγRIIIa-158 (CD16) is known to improve clinical response to rituximab in indolent non-Hodgkin’s 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 (ADCC). We observed higher levels of FcγRIIIa transcripts among individuals with the FcγRIIIa-158 V/V versus -V/F or -F/F genotype (p<0.001); 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=0.029), as well as augmented rituximab binding and rituximab-dependent ADCC activity. 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. For personal use only. on January 10, 2018. by guest www.bloodjournal.org From