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

R. Kapur, L. Della Valle, O.J. Verhagen, A. Hipgrave Ederveen, P. Ligthart, M. de Haas, B. Kumpel, M. Wuhrer, C.E. van der Schoot, G. Vidarsson

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Abstract

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.
Original languageEnglish
JournalTransfusion
DOIs
Publication statusPublished - 2015

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    Kapur, R., Della Valle, L., Verhagen, O. J., Hipgrave Ederveen, A., Ligthart, P., de Haas, M., ... Vidarsson, G. (2015). Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D. Transfusion. https://doi.org/10.1111/trf.12880