Prophylaxis to prevent alloimmunization and FNAIT

In this project we explore the potential for using monoclonal anti-HPA-1a antibodies as prophylaxis to prevent alloimmunization and subsequent FNAIT.

Here, we test different designed variants of the monoclonal anti-HPA-1a mAb 26.4 - previously developed in our research group - for its efficacy to induce antibody mediated immune suppression (AMIS) and thus prevent alloimmunization. The in vitro studies encompass characterization of functionality of the different antibody variants. The in vivo studies is based on a murine model of alloimmunization with humanized platelets antigens. The AMIS experiments are based on prophylactic treatment prior to platelet transfusion, and resulting in rapid depletion of the transfused platelets limiting the mounting of an immune response againt the platelet antigens.

Publications related to this project:

Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia in Mice: Biochemical and Cell Biological Characterization of Isoforms of a Human Monoclonal Antibody. Mortberg TV, Zhi H, Vidarsson G, Foss S, Lissenberg-Thunnissen S, Wuhrer M, Michaelsen TE, Skogen B, Stuge TB, Andersen JT, Newman PJ, Ahlen MT. Immunohorizons. 2022;6:90-103 https://doi.org/10.4049/immunohorizons.2100097

Murine models for studying treatment, prevention and pathogenesis of FNAIT. Rasmussen TV and Ahlen MT. Transfusion and Apheresis Science. 2020; 59;1:102706 https://doi.org/10.1016/j.transci.2019.102706

Previous relevant publications underpinning the project:

High-resolution mapping of the polyclonal immune response to the human platelet alloantigen HPA-1a (Pl^A1). Zhi H, Ahlen MT, Thinn AMM, Weiler H, Curtis BR, Skogen B, Zhu J, Newman PJ. Blood Adv. 2018;13;2(21):3001-3011. https://doi.org/10.1182/bloodadvances.201802334

Characterization of a Human Platelet Antigen-1a-Specific Monoclonal Antibody Derived from a B Cell from a Woman Alloimmunized in Pregnancy. Eksteen M, Tiller H, Averina M, Heide G, Kjaer M, Ghevaert C, Michaelsen TE, Ihle O, Husebekk A, Skogen B, Stuge TB. J Immunol. 2015;194: 5751-5760. https://doi.org/10.4049/jimmunol.1401599

Toward a prophylaxis against fetal and neonatal alloimmune thrombocytopenia: induction of antibody-mediated immune suppression and prevention of severe clinical complications in a murine model. Tiller H, Killie MK, Chen P, Eksteen M, Husebekk A, Skogen B, Kjeldsen-Kragh J, Ni H. Transfusion. 2012;52:1446-1457. https://doi.org/10.1111/j.1537-2995.2011.03480.x

Members:

Maria Therese Ahlen

Tor Brynjar Stuge

Bjørn Skogen

Trude Victoria Rasmussen

Financial/grant information:

The project has funding from Helse Nord and UiT the Arctic University of Norway.