Prophylactic anti‐D preparations display variable decreases in F c‐fucosylation of anti‐D
R Kapur, L Della Valle, OJHM Verhagen… - …, 2015 - Wiley Online Library
R Kapur, L Della Valle, OJHM Verhagen, A Hipgrave Ederveen, P Ligthart, M de Haas…
Transfusion, 2015•Wiley Online LibraryBackground RhIG is obtained from hyperimmunized healthy anti‐D donors (HIDs) boosted
with D+ red blood cells (RBC s). One hypothesis for its mechanism of action is fast clearance
of opsonized D+ RBCs through F cγ receptor (FcγR) III. Levels of immunoglobulin (Ig) GF c‐
fucosylation influence interactions with FcγRIII, with less F c‐fucosylation strengthening the
interaction. Study Design and Methods Anti‐D IgG 1 F c‐glycosylation patterns in 93 plasma
samples from 28 male and 28 female D utch HID s and RhIG were analyzed with mass …
with D+ red blood cells (RBC s). One hypothesis for its mechanism of action is fast clearance
of opsonized D+ RBCs through F cγ receptor (FcγR) III. Levels of immunoglobulin (Ig) GF c‐
fucosylation influence interactions with FcγRIII, with less F c‐fucosylation strengthening the
interaction. Study Design and Methods Anti‐D IgG 1 F c‐glycosylation patterns in 93 plasma
samples from 28 male and 28 female D utch HID s and RhIG were analyzed with mass …
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.
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