Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg]
Red blood cells (RBCs) from a rhesus D (RhD)-positive fetus that reach the bloodstream of an RhD-negative pregnant woman during birth can induce a pathogenic antibody (Ab) response against the RhD-positive RBCs, leading to fetal hemolytic disease in subsequent pregnancies. To prevent a pathogenic im...
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doaj-62fa9e8e0acb44a4a15cf019e7ca6f952020-11-25T03:31:46ZengF1000 Research LtdF1000Research2046-14022013-08-01210.12688/f1000research.2-169.v11852Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg]André Winkler0Markus Berger1Marc Ehlers2Laboratory of Tolerance and Autoimmunity, Institute for Systemic Inflammation Research, University of Luebeck, Luebeck, 23538, GermanyLaboratory of Glycodesign and Glycoanalytics, Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité – University Medicine Berlin, Berlin, 10117, GermanyLaboratory of Tolerance and Autoimmunity, Institute for Systemic Inflammation Research, University of Luebeck, Luebeck, 23538, GermanyRed blood cells (RBCs) from a rhesus D (RhD)-positive fetus that reach the bloodstream of an RhD-negative pregnant woman during birth can induce a pathogenic antibody (Ab) response against the RhD-positive RBCs, leading to fetal hemolytic disease in subsequent pregnancies. To prevent a pathogenic immune reaction, the RhD-negative mother receives serum immunoglobulin G (IgG) containing polyclonal RhD-specific IgG Abs that is purified from healthy RhD-negative men immunized with RhD-positive RBCs. However, the protective mechanism of these polyclonal RhD-specific IgG Abs is unclear. It has become increasingly clear that the effector function of IgG Abs is regulated by the glycan pattern linked to the Fc region of IgG Abs. Non-fucosylated (afucosylated) IgG Abs have a higher affinity for activating Fc gamma receptors, and thus induce a stronger Ab-dependent cellular cytotoxicity (ADCC) reaction than do fucosylated IgG Abs. Agalactosylated and asialylated, autoantigen-specific serum IgG Abs correlate with pro-inflammatory immune responses and disease activity in patients with rheumatoid arthritis. In contrast, galactosylated and sialylated IgG Abs are immunosuppressive and inhibit in form of immune complexes (ICs) dendritic cell (DC) maturation and pro-inflammatory T and B cell immune responses in an antigen-specific manner. However, the galactosylation and sialylation levels of the protective polyclonal RhD-specific IgG Abs are unknown. Here, we purified RhD-specific IgG Abs from the approved commercial product Rhophylac® (CSL Behring) and found that these RhD-specific IgG Abs were even more galactosylated and sialylated than the total Rhophylac® IgG Abs. This result suggests that these galactosylated and sialylated polyclonal RhD-specific IgG Abs are immunosuppressive and induce tolerance against RhD, which would be in strong contrast to a low fucosylated, low galactosylated and low sialylated monoclonal RhD-specific IgG Ab developed to prevent fetal hemolytic disease that has recently passed a clinical phase II study.http://f1000research.com/articles/2-169/v1ImmunomodulationReproductive Immunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
André Winkler Markus Berger Marc Ehlers |
spellingShingle |
André Winkler Markus Berger Marc Ehlers Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg] F1000Research Immunomodulation Reproductive Immunology |
author_facet |
André Winkler Markus Berger Marc Ehlers |
author_sort |
André Winkler |
title |
Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg] |
title_short |
Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg] |
title_full |
Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg] |
title_fullStr |
Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg] |
title_full_unstemmed |
Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies [v1; ref status: indexed, http://f1000r.es/1fg] |
title_sort |
anti-rhesus d prophylaxis in pregnant women is based on sialylated igg antibodies [v1; ref status: indexed, http://f1000r.es/1fg] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2013-08-01 |
description |
Red blood cells (RBCs) from a rhesus D (RhD)-positive fetus that reach the bloodstream of an RhD-negative pregnant woman during birth can induce a pathogenic antibody (Ab) response against the RhD-positive RBCs, leading to fetal hemolytic disease in subsequent pregnancies. To prevent a pathogenic immune reaction, the RhD-negative mother receives serum immunoglobulin G (IgG) containing polyclonal RhD-specific IgG Abs that is purified from healthy RhD-negative men immunized with RhD-positive RBCs. However, the protective mechanism of these polyclonal RhD-specific IgG Abs is unclear. It has become increasingly clear that the effector function of IgG Abs is regulated by the glycan pattern linked to the Fc region of IgG Abs. Non-fucosylated (afucosylated) IgG Abs have a higher affinity for activating Fc gamma receptors, and thus induce a stronger Ab-dependent cellular cytotoxicity (ADCC) reaction than do fucosylated IgG Abs. Agalactosylated and asialylated, autoantigen-specific serum IgG Abs correlate with pro-inflammatory immune responses and disease activity in patients with rheumatoid arthritis. In contrast, galactosylated and sialylated IgG Abs are immunosuppressive and inhibit in form of immune complexes (ICs) dendritic cell (DC) maturation and pro-inflammatory T and B cell immune responses in an antigen-specific manner. However, the galactosylation and sialylation levels of the protective polyclonal RhD-specific IgG Abs are unknown. Here, we purified RhD-specific IgG Abs from the approved commercial product Rhophylac® (CSL Behring) and found that these RhD-specific IgG Abs were even more galactosylated and sialylated than the total Rhophylac® IgG Abs. This result suggests that these galactosylated and sialylated polyclonal RhD-specific IgG Abs are immunosuppressive and induce tolerance against RhD, which would be in strong contrast to a low fucosylated, low galactosylated and low sialylated monoclonal RhD-specific IgG Ab developed to prevent fetal hemolytic disease that has recently passed a clinical phase II study. |
topic |
Immunomodulation Reproductive Immunology |
url |
http://f1000research.com/articles/2-169/v1 |
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