Mechanisms of anti-αIIb mediated miscarriage in fetal and neonatal alloimmune thrombocytopenia

Platelets are small blood cells well-recognized as being essential to stop bleeding. To perform their functions, platelets express majority integrin heterodimer αIIbβ3, which synchronize with other receptors on the surface, to form a blood clot. In fetal and neonatal alloimmune thrombocytopenia (FNAIT), paternally-inherited platelet receptors in fetus are identified as “foreign antigens” by the mother’s immune system during pregnancy, generating anti-fetal platelet antigen antibodies that target fetus cells. The life threatening consequences include severe bleeding (e.g. intracranial hemorrhage), and/or impaired development. In our animal model of aΙΙbmediated FNAIT, our lab interestingly observed evidences of antibody depleting fetal αIIb-expressing hematopoietic stem cells (HSCs) and blocking their migration, which disrupts fetal liver and bone marrow development. Poor embryonic development causing death (miscarriage) may explain for why there is a paucity of anti-αIIb mediated FNAIT cases reported. In this proposal, I will further investigate the mechanisms of αIIbmediated FNAIT to understand how αIIb- expressing HSCs are cleared and/or have impaired migration in FNAIT, associating with higher incidence of miscarriage. This study is novel and will provide significant insights in the fields of transfusion medicine, HSC engraftment, improved current diagnostic and therapeutic strategies to control this life-threatening disease and save lives.

NI, Heyu

St. Michael's Hospital

Graduate Fellowship Program

Ontario

$52,000