Unexpected suppression of anti‐Fy<sup>a</sup> and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin

Branch, Donald R.; Scofield, Terry L.; Moulds, John J.; Swanson, Jane L.

doi:10.1111/j.1537-2995.2010.02905.x

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…As stated above, the working mechanism of RhIG has not been elucidated yet. There is also clear evidence for an immunomodulatory activity of RhIG, demonstrated by immunosuppression of anti‐Fya antibody responses in pregnancy in D– women and increased levels of immunomodulatory cytokines like transforming growth factor‐β and prostaglandin E2 after RhIG administration . It might be speculated that glycosylation level of RhIG, of which the fucosylation is the most striking feature, also affects these immunomodulatory properties.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…Her anti-Fy a titer was observed to decrease dramatically following the administration of multiple doses of prophylactic antenatal RhIG. 29 …”

Section: Discussionmentioning

confidence: 99%

“…One published case report additionally suggests a possible non‐D‐specific suppressive effect of RhIG. Branch and colleagues reported a case of a pregnant woman with a high‐titer anti‐Fy a . Her anti‐Fy a titer was observed to decrease dramatically after the administration of multiple doses of prophylactic antenatal RhIG.…”

Section: Discussionmentioning

confidence: 99%

Does Rh immune globulin suppress HLA sensitization in pregnancy?

et al. 2012

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BACKGROUND How Rh immune globulin (RhIG) prevents sensitization to D antigen is unclear. If RhIG Fc delivers a nonspecific immunosuppressive signal, then RhIG may inhibit sensitization to antigens other than D. HLA antibody prevalence was compared in previously pregnant RhD negative versus RhD positive women to investigate whether RhIG suppresses HLA sensitization. STUDY DESIGN AND METHODS In the Leukocyte Antibody Prevalence Study (LAPS)1, 7,920 volunteer blood donors were screened for anti-HLA antibodies and surveyed about prior pregnancies and transfusions. A secondary analysis of the LAPS database was performed. RESULTS RhD negative women ≤40 years old (presumed to have received antenatal ± postpartum RhIG in all pregnancies) had a significantly lower HLA sensitization rate than RhD positive women (RR 0.58, 95% CI 0.40–0.83). When stratified by deliveries (1, 2, 3, or ≥4), RhD negative women ≤40 were HLA sensitized less often than RhD positive women in every case. In contrast, a clear relationship between RhD type and HLA sensitization was not seen in older previously pregnant women whose childbearing years are presumed to have preceded the use of routine RhIG prophylaxis. In a multivariable logistic regression model, RhD negative women ≤40 years old remained significantly less likely to be HLA sensitized compared with RhD positive women after adjusting for parity, time from last pregnancy, lost pregnancies, and transfusions (OR 0.55, 95% CI 0.34–0.88). CONCLUSION Consistent with a nonspecific immunosuppressive effect of RhIG, younger previously pregnant RhD negative women were less likely than previously pregnant RhD positive women to be HLA sensitized.

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“…Of note, it was reported that the YB2/0 form of a mAb-D, T125, had greater interactions with both FcγRIIIa and FcγRIIb than the CHO form, thus indicating that low fucosylated anti-D would be effective in this mechanism of B cell suppression 82 as well as in rapid RBC clearance 29 . (e) Other "non-specific" immunomodulatory effects of prophylactic anti-D could be caused by the anti-D or many other alloantibodies in the donor pool of immuno-globulins (similar to IVIG) using these mechanisms, such as reductions of anti-Fy a in a case report 83 and of anti-HLA sensitisation in a large survey 84 . HLA class I antigens (Bg) are expressed on most cells including RBC of some normal donors 85 .…”

Section: Summary Of Clearancementioning

confidence: 99%

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Kumpel

Saldova

Koeleman

et al. 2020

Sci Rep

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Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in fcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADcc activity. In vivo, two B mAb-Ds with 77-81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with <50% fucosylation mediated more efficient ADCC and clearance than anti-D Ig. Galactosylation of B mAb-Ds was 57-83% but 15-58% for rodent mAb-Ds. HH mAb-Ds had non-human sugars. These data reveal high galactosylation like anti-D Ig (>60%) together with lower fucosylation (<60%) as safe features of mAb-Ds for mediating rapid red cell clearance at low doses, to enable effective, inexpensive prophylaxis.

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Unexpected suppression of anti‐Fy^a and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin

Cited by 7 publications

References 13 publications

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

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

Does Rh immune globulin suppress HLA sensitization in pregnancy?

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

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Unexpected suppression of anti‐Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin

Cited by 7 publications

References 13 publications

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

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

Does Rh immune globulin suppress HLA sensitization in pregnancy?

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Contact Info

Product

Resources

About

Unexpected suppression of anti‐Fy^a and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin