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

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...

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Bibliographic Details
Published in:Transfusion (Philadelphia, Pa.) Pa.), 2015-03, Vol.55 (3), p.553-562
Main Authors: Kapur, Rick, Della Valle, Luciana, Verhagen, Onno J.H.M., Hipgrave Ederveen, Agnes, Ligthart, Peter, de Haas, Masja, Kumpel, Belinda, Wuhrer, Manfred, van der Schoot, C. Ellen, Vidarsson, Gestur
Format: Article
Language:English
Subjects:
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
Medical research
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
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Summary: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.
ISSN:0041-1132
1537-2995
DOI:10.1111/trf.12880