Grant: Operating Grant

Platelets are small blood cells that are responsible for the arrest of bleeding at the site of vessel injury. A low platelet count is called thrombocytopenia. Antibodies to fetal platelets can be induced in the mother by proteins called antigens on platelets, which are inherited from the father but lacking in the mother. These maternal antibodies can cross the placenta and damage fetal platelets leading to a disease called Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT). This disease occurs in 0.5-1.5/1,000 liveborn neonates. It may also cause miscarriage. The major risk associated with FNAIT is severe bleeding, particularly in the brain (intracranial haemorrhage), leading to neurological impairment or death. Currently, the pathogenesis of FNAIT is largely unknown and effective therapy is not available. We plan to use our newly developed FNAIT mouse models to study: 1) how a mother generates antibodies to different fetal platelet antigens, and how miscarriage can occur in this disease; 2) whether these antibodies also target and injure fetal vessels, which may enhance bleeding and inhibit fetal growth; and 3) whether we can prevent this disease by inducing immune suppression in the mother and how we can treat it more efficiently by using IVIG and anti-FcRn therapies. This study will provide significant information for both the pathogenesis and treatment of FNAIT.