Mechanism of increased efficacy of recombinant Fc-μTP-L309C compared to IVIg to ameliorate mouse immune thrombocytopenia

eJHaem

article

Bonnie J.B. Lewis¹  Beth Binnington¹  Megan Blacquiere¹  Rolf Spirig³  Fabian Käsermann³  Donald R. Branch¹ 

[1] Donald R. Branch, BS, MT,(ASCP)SBB, PhD, Donald R. Branch, BS, MT,(ASCP)SBB, PhD, 30 Bond Street, Keenan Research Centre;Department of Laboratory Medicine and Pathobiology, University of Toronto;Research, CSL Biologics Research Center;Department of Medicine, University of Toronto

关键词: immune thrombocytopenia;    immunotherapy;    ITP;    ITP intravenous immunoglobulin;    IVIG;    IVIg;    recombinant Fc hexamer;   

DOI  :  10.1002/jha2.304

来源: Wiley

【 摘 要 】

Recombinant Fc-μTP-L309C is more efficacious than intravenous immunoglobulin (IVIg) at ameliorating antibody-mediated autoimmune diseases through its effects on Fcγ receptors (FcγRs). Fc-μTP-L309C inhibited in-vitro FcγR-mediated phagocytosis 10 4 /10 5 -fold better than IVIg. Fc-μTP-L309C, given subcutaneously, recovered platelet counts in an immune thrombocytopenia (ITP) mouse model to a higher degree than IVIg at a 10-fold lower dose. We show, using confocal microscopy, that Fc-μTP-L309C binds to monocyte-macrophages and is rapidly internalized, whereas, IVIg remains on the cell surface. Western blotting showed that internalized FcγRIII is degraded through a lysosomal pathway, and this reduction of cell surface FcγRIII is likely responsible for the increased efficacy to ameliorate ITP.

【 授权许可】

Unknown