In autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) autoantibodies are formed against respectively red blood cells or platelets. The opsonized blood cells are cleared by macrophages in the spleen via the interaction with FcγRs (receptors that recognize the Fc part of IgGs). Treatment of these diseases consists of intravenous administration of high dose immunoglobulin (Intravenous Immunoglobulin; IVIg). The exact working mechanism of IVIg is still unresolved, but a widely believed hypothesis is that IVIg blocks the FcγRs on the macrophage surface and thereby prevents the uptake of red blood cells or platelets.
We have set up an assay to study the phagocytosis of opsonized red blood cells in vitro and we have shown that the administration of IgG prior to phagocytosis blocks the uptake of erythrocytes in a dose dependent manner.
In this project we will focus on IgG glycosylation and the interaction with FcγRs. It is known that IgG glycosylation changes the affinity to the different FcγRs. We will therefore investigate whether differently glycosylated antibodies can block the phagocytosis of opsonized red blood cells to different extent. Knowledge on IgG glycosylation and FcγR interactions could potentially ameliorate IVIg treatment.
Techniques: Blood cell isolation, cell culture, phagocytosis assays, flow cytometry
U verlaat de website van Sanquin. Links naar andere sites worden u aangeboden als een service. Sanquin draagt geen verantwoordelijkheid voor hun inhoud.