Anti-RhD antibody therapy modulates human natural killer cell function

Anti-RhD antibodies are widely used in clinical practice to prevent immunization against RhD, principally in hemolytic disease of the fetus and newborn. Intriguingly, this disease is induced by production of the very same antibodies when an RhD negative woman is pregnant with an RhD positive fetus. Despite over five decades of use, the mechanism of this treatment is, surprisingly, still unclear. Here we show that anti-RhD antibodies induce human natural killer (NK) cell degranulation. Mechanistically, we demonstrate that NK cell degranula-tion is mediated by binding of the Fc segment of anti-RhD antibodies to CD16, the main Fc gamma receptor expressed on NK cells. We found that this CD16 activation is dependent upon glycosylation of the anti-RhD anti-bodies. Furthermore, we show that anti-RhD antibodies induce NK cell degranulation in vivo in patients who receive this treatment prophylacti-cally. Finally, we demonstrate that the anti-RhD drug KamRho enhances the killing of dendritic cells. We suggest that this killing leads to reduced activation of adaptive immunity and may therefore affect the production of anti-RhD antibodies

Automated summary

Anti-RhD antibodies are used to prevent RhD immunization, potentially by inducing NK cell degranulation. The mechanism involves CD16 activation and glycosylation of the antibodies. Additionally, the RhD drug may enhance killing of dendritic cells.