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dc.contributor.authorMørtberg, Trude Victoria
dc.contributor.authorZhi, Huiying
dc.contributor.authorVidarsson, Gestur
dc.contributor.authorFoss, Stian
dc.contributor.authorLissenberg-Thunnissen, Suzanne
dc.contributor.authorWuhrer, Manfred
dc.contributor.authorMichaelsen, Terje Einar
dc.contributor.authorSkogen, Bjørn
dc.contributor.authorStuge, Tor Brynjar
dc.contributor.authorAndersen, Jan Terje
dc.contributor.authorNewman, Peter J.
dc.contributor.authorAhlen, Maria Therese
dc.description.abstractMaternal alloantibodies toward paternally inherited Ags on fetal platelets can cause thrombocytopenia and bleeding complications in the fetus or neonate, referred to as fetal and neonatal alloimmune thrombocytopenia (FNAIT). This is most commonly caused by Abs against the human platelet Ag (HPA)-1a in Caucasians, and a prophylactic regimen to reduce the risk for alloimmunization to women at risk would be beneficial. We therefore aimed to examine the prophylactic potential of a fully human anti–HPA-1a IgG1 (mAb 26.4) with modified Fc region or altered N-glycan structures. The mAb 26.4 wild-type (WT) variants all showed efficient platelet clearance capacity and ability to mediate phagocytosis independent of their N-glycan structure, compared with an effector silent variant (26.4.AAAG), although the modified N-glycan variants showed differential binding to FcγRs measured in vitro. In an in vivo model, female mice were transfused with platelets from transgenic mice harboring an engineered integrin β3 containing the HPA-1a epitope. When these preimmunized mice were bred with transgenic males, Abs against the introduced epitope induced thrombocytopenia in the offspring, mimicking FNAIT. Prophylactic administration of the mAb 26.4.WT, and to some extent the mAb 26.4.AAAG, prior to platelet transfusion resulted in reduced alloimmunization in challenged mice and normal platelet counts in neonates. The notion that the effector silent variant hampered alloimmunization demonstrates that rapid platelet clearance, as seen with mAb 26.4.WT, is not the sole mechanism in action. Our data thus successfully demonstrate efficient Ab-mediated immunosuppression and prevention of FNAIT by anti–HPA-1a monoclonal variants, providing support for potential use in humans.en_US
dc.identifier.citationMørtberg, Zhi, Vidarsson, Foss, Lissenberg-Thunnissen, Wuhrer, Michaelsen, Skogen, Stuge, Andersen, Newman, Ahlen. Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia in Mice: Biochemical and Cell Biological Characterization of Isoforms of a Human Monoclonal Antibody. ImmunoHorizons. 2022;6(1):99-103en_US
dc.identifier.cristinIDFRIDAID 2060528
dc.publisherAmerican Association of Immunologistsen_US
dc.relation.ispartofMørtberg, T.V. (2023). Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) by prophylactic monoclonal antibodies. In vitro and preclinical evaluation of HPA-1a-specific antibodies. (Doctoral thesis). <a href=></a>.
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titlePrevention of Fetal/Neonatal Alloimmune Thrombocytopenia in Mice: Biochemical and Cell Biological Characterization of Isoforms of a Human Monoclonal Antibodyen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)