Reducing IVIG usage by developing novel prophylaxis therapies against FNAIT

Fetal and Neonatal Alloimmune thrombocytopenia (FNAIT) is a relatively common (~1 in 1000 live births), life-threatening disorder caused by maternal antibodies against paternally-inherited fetal platelet antigens. These antibodies cross the placenta and can cause miscarriage and severe bleeding, especially in the fetal brain. Intravenous Immunoglobulin (IVIG), a major blood product of Canadian Blood Services, is usually administered to the mother in high doses during pregnancy to prevent FNAIT. Maternal antibodies frequently target the β3 subunit of platelet surface glycoprotein GPIIbIIIa (i.e αIIbβ3 integrin) essential for platelet aggregation to stop bleeding. Our laboratory established the first animal model of FNAIT. We also generated polyclonal/monoclonal anti-β3 antibodies (CBS patent) that bind both human and mice β3. I propose that our antibodies, similar to anti-D antibodies in hemolytic disease, can induce Antibody- Mediated Immune Suppression (AMIS) and prevent the maternal immune response against paternal mismatched antigens. Secondly, deglycosylated anti-β3 antibodies can bind neonatal Fc receptor (FcRn) and cross placenta but do not bind Fc receptors (FcRs) on macrophage, thus competitively block maternal pathogenic antibody-mediated platelet clearance. This research has the great potential to develop novel prophylaxis and therapeutics against FNAIT, which will spare valuable blood products including both IVIG and platelets for fetal/neonatal transfusion.

NI, Heyu

St. Michael's Hospital

Postdoctoral Fellowship Program

Ontario

$165,000