Fc receptors and IVIg in ITP

Canada is not self-sufficient for plasma donation for IVIg and only meets 18% of the demand. We need to better understand how IVIg works as well as proactively replace IVIg with a recombinant product (RPA2&5). We have proposed that IVIg can be replaced by a recombinant single-chain antibody which binds and blocks Fc receptor IIIA involved in mouse autoimmune disease. While this work is progressing well, we unfortunately do not understand which Fc receptors are actually involved in the plateletautoimmune
disease (immune thrombocytopenia (ITP)) as well as patients with other autoimmune diseases. The objective of this grant is to gain an understanding of which Fc receptors (Fc receptor I vs II vs III) are involved in platelet destruction in ITP. The grant will explore the ability of ITP patient sera to trigger phagocytosis by human splenic macrophages mediated by each of the major Fc receptors both in vitro as well as perform in vivo work with patient ITP sera using a humanized-mouse model of ITP. At the conclusion of this grant we will have learned which Fc receptors are involved in platelet destruction in ITP which can be used to design an effective pharmacologic strategy to block the appropriate Fc receptors.
Principal Investigator / Supervisor
LAZARUS, Alan
Co-Investigator(s) / Trainee
CSERTI-GAZDEICH, Christine LIN, Yulia CALLUM, Jeannie SHOLZBERG, Michelle NI, Heyu
Institution
Canadian Blood Services
Program
Intramural Research Grant Program
Province
Ontario
Total Amount Awarded
$432,000
Project Start Date
Project End Date