Platelet desialylation: novel mechanism of platelet clearance and immune tolerance

Platelets are anucleate blood cells that play key roles in hemostasis. I recently published a novel Fc-independent platelet clearance mechanism in immune thrombocytopenia (ITP), whereby antibody-mediated platelet desialylation (loss of terminal sialic acid) led to platelet clearance in the liver via Ashwell-Morell receptors (Haematologica 2014, Nature Communications 2015). Beyond ITP, how this desialylated clearance in the liver may modulate the immune response has never been investigated. Given that the liver is an important site of peripheral immune tolerance (e.g. oral food antigens) increased desialylated platelet clearance here may dampen the immune response against platelets or other antigens. My preliminary data shows transfusion of neuraminidase treated WT-platelets (desialylated) into platelet antigen knock-out mice (GPIb-/- or GPIIIa-/-) leads to decreased anti-platelet-antibody response compared to response against non-neuraminidase-treated platelets. Further studies into the immunosuppressive potential of desialylated platelet clearance in the liver may be useful in designing novel approaches to minimize alloimmunization from blood products during transfusions. Conversely, the rapid clearance of desialylated platelets from circulation is undesirable in platelet transfusions. Platelets naturally undergo desialylation during storage, I aim to study whether inhibition of this process with sialidase inhibitors may improve the quality of stored platelets. Both these aims fit the goal of Canadian Blood Services to minimize adverse effects and improve quality of blood transfusions

NI, Heyu

University of Toronto

Graduate Fellowship Program

Ontario

$104,000