For example, rituximab-mediated targeting of CD20+ tumor cells results in potent downregulation of NK cell CD16 that is dependent on MMP9-mediated cleavage (13, 14); exposure of NK cells to HCMV-infected fibroblasts leads to loss of CD16 concurrent with increased degranulation (9); MMP-dependent downregulation of CD16 is a feature of chronic HIV-1 infection (16, 17); and soluble NK cell-derived CD16 is elevated during rheumatoid arthritis, a chronic immune complex-associated inflammatory disease (18). This evidence concerns the gene FCGR3A and rheumatoid arthritis.