Anti-RhD antibody therapy modulates human natural killer cell function

Haematologica. 2021 Jul 1;106(7):1846-1856. doi: 10.3324/haematol.2019.238097.

Abstract

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 degranulation is mediated by binding of the Fc segment of anti-RhD antibodies to CD16, the main Fcγ receptor expressed on NK cells. We found that this CD16 activation is dependent upon glycosylation of the anti-RhD antibodies. Furthermore, we show that anti-RhD antibodies induce NK cell degranulation in vivo in patients who receive this treatment prophylactically. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Fetus / metabolism
  • Glycosylation
  • Humans
  • Infant, Newborn
  • Killer Cells, Natural*
  • Lymphocyte Activation
  • Pregnancy
  • Receptors, IgG* / metabolism

Substances

  • Receptors, IgG

Grants and funding

Funding: This work was supported by the ISF-China program and by the ISF Moked grant. Further support came from the ICRF professorship grant, by the MOST-DKFZ grant, by the GIF grant. The study was also supported by the Israel Science Foundation (grant 502/15), the Kass Medical Research Award and the Israeli Society of Hematology and Transfusion Medicine research grant (to S.E).