Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D

Transfusion. 2015 Mar;55(3):553-62. doi: 10.1111/trf.12880. Epub 2014 Sep 19.


Background: RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with FcγRIII, with less Fc-fucosylation strengthening the interaction.

Study design and methods: Anti-D IgG1 Fc-glycosylation patterns in 93 plasma samples from 28 male and 28 female Dutch HIDs and RhIG were analyzed with mass spectrometry. The Fc-glycosylation profiles of HIDs were evaluated with regard to their immunization history.

Results: HID sera demonstrated clearly lowered anti-D Fc-fucosylation compared to normal IgG fucosylation (93%); this was more pronounced for female than for male HIDs (47% vs. 65%, p = 0.001). RhIG preparations from seven manufacturers varied greatly in the level of Fc-fucosylation (56%-91%). The level of fucosylation slightly increased upon repeated immunization, although it remained fairly constant over time. The RhIG from the different manufacturers all demonstrated increased Fc-galactosylation (64%-82%) compared to total IgG (38%-51%).

Conclusion: RhIG preparations vary in Fc-fucosylation and all demonstrate increased galactosylation. Despite not knowing the exact working mechanism, immunoprophylaxis could perhaps be optimized by selection of donors whose anti-D have low amounts of Fc-fucose, to increase the clearance activity of anti-D preparations, as well as high amounts of galactosylation, for anti-inflammatory effects. Implementing a biologic assay in the standardization of RhIG preparations might be considered.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Blood Donors
  • Female
  • Fucose / blood*
  • Galactose / blood
  • Glycosylation
  • Humans
  • Immunization
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin G / chemistry*
  • Immunoglobulin G / isolation & purification
  • Isoantibodies / chemistry*
  • Isoantibodies / isolation & purification
  • Male
  • Middle Aged
  • Pregnancy
  • Protein Processing, Post-Translational
  • Receptors, IgG / metabolism
  • Rh Isoimmunization / therapy
  • Rho(D) Immune Globulin
  • Sex Characteristics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • FCGR3A protein, human
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Isoantibodies
  • RHO(D) antibody
  • Receptors, IgG
  • Rho(D) Immune Globulin
  • Fucose
  • Galactose