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

Abstract

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.

Glycosylation pattern of anti‐platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

“…IgG-Fc-glycosylation has a role in determining binding affinities to the receptors in myeloid cells and the observed specific IgG-Fc glycosylation features in both anti-red blood cell and anti-platelet IgG mediated alloimmune diseases Kapur et al, 2014aKapur et al, ,b, 2015b. This is particularly true for Fc-fucosylation in regulating the affinity of IgG to FccRIIIa and FccRIIIb, but our results also suggest galactosylation to strongly affect disease severity.…”

“…The primary factor for the skewed fucosylation pattern is not likely to be the pregnancy itself because this response was also observed in male hyperimmunized anti-D donors, although the level of fucosylation was slightly higher in the men (Kapur et al, 2015b). This particular type of response seems therefore to be more dictated by the nature of these antigens, which are particulate, cell-bound and blood-borne antigens for both anti-D and HPA-1a.…”

“…Given that these glycan features of the antigen-specific antibodies, particularly core-fucosylation, are unique compared to the profile observed in total IgG, and seem to predict the clinical outcome in FNAIT and HDFN (Kapur et al, 2014a(Kapur et al, ,b, 2015b, we next analysed Fc-glycosylation of anti-HPA-1a IgG in different phases during and after pregnancy. No significant differences in mean ranking of the percentage of Fc-fucosylation, Fc-bisection, Fc-galactosylation or Fc-sialylation of anti-HPA-1a IgG1 were found comparing different trimesters and postpartum samples (Fig 3).…”

Antigen modulation as a potential mechanism of anti-KEL immunoprophylaxis in mice

“…Although in widespread use for .50 years, its mechanism of action remains poorly understood. 7,8 Further, differences in fucosylation patterns of RhIg by manufacturer have recently been described, 9 with these differences theoretically being capable of impacting efficacy. 10 The desire to understand the mechanism of action of RhIg is multifold: (1) a more standard RhIg product 9 could potentially be developed, be it a polyclonal anti-D preparation from volunteer donors or a monoclonal anti-D or monoclonal cocktail developed in a laboratory 11,12 ; and (2) There is an Inside Blood Commentary on this article in this issue.…”

Hemolytic Disease of the Fetus and Newborn: Modern Practice and Future Investigations

“…For example, differences in fucosylation patterns have recently been identified between brands of RhIg, with these patterns theoretically impacting product efficacy by altering Fcγ binding 47 .…”