Anti-RhD antibody therapy modulates human natural killer cell function

Shlomo Elias, Inbal Kol, Shira Kahlon, Rajaa Amore, Mariam Zeibak, Dror Mevorach, Uriel Elchalal, Orly Zelig, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1846-1856
Number of pages11
JournalHaematologica
Volume106
Issue number7
DOIs
StatePublished - 1 Jul 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Ferrata Storti Foundation

Fingerprint

Dive into the research topics of 'Anti-RhD antibody therapy modulates human natural killer cell function'. Together they form a unique fingerprint.

Cite this