Dr Cedric Ghevaert

Development of new therapeutics for platelet alloimmune disorders.

This project funded by the NHSBT, looks at developing new diagnostic and therapeutic approaches in the context of fetomaternal alloimmune thrombocytopenia (FMAIT). This is a disease that affects fetuses and newborns, in which the platelet count is decreased by antibodies specific for platelet antigens (fetal Human Platelet Antigen-1a (HPA-1a) ) inherited from the father but which are absent in the mother. FMAIT can result in intracranial haemorrhage and intrauterine death. This disorder affects 1/1200 pregnancies in the UK and leads in 10-20% of fetus/neonates affected to severe brain haemorrhage. We have developed a therapeutic human recombinant high affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fc gamma receptors. In the first-in-man study, we demonstrate the therapeutic potential of B2G1Δnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunisation in HPA-1a negative mothers.