PMID- 35845218 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220719 IS - 2688-6146 (Electronic) IS - 2688-6146 (Linking) VI - 2 IP - 4 DP - 2021 Nov TI - Mechanism of increased efficacy of recombinant Fc-muTP-L309C compared to IVIg to ameliorate mouse immune thrombocytopenia. PG - 789-793 LID - 10.1002/jha2.304 [doi] AB - Recombinant Fc-muTP-L309C is more efficacious than intravenous immunoglobulin (IVIg) at ameliorating antibody-mediated autoimmune diseases through its effects on Fcgamma receptors (FcgammaRs). Fc-muTP-L309C inhibited in-vitro FcgammaR-mediated phagocytosis 10(4)/10(5)-fold better than IVIg. Fc-muTP-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-muTP-L309C binds to monocyte-macrophages and is rapidly internalized, whereas, IVIg remains on the cell surface. Western blotting showed that internalized FcgammaRIII is degraded through a lysosomal pathway, and this reduction of cell surface FcgammaRIII is likely responsible for the increased efficacy to ameliorate ITP. CI - (c) 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd. FAU - Lewis, Bonnie J B AU - Lewis BJB AD - Donald R. Branch, BS, MT(ASCP)SBB, PhD Donald R. Branch, BS, MT(ASCP)SBB, PhD 30 Bond Street, Keenan Research Centre Toronto M5B 1W8 Canada. AD - Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Canada. FAU - Binnington, Beth AU - Binnington B AD - Donald R. Branch, BS, MT(ASCP)SBB, PhD Donald R. Branch, BS, MT(ASCP)SBB, PhD 30 Bond Street, Keenan Research Centre Toronto M5B 1W8 Canada. FAU - Blacquiere, Megan AU - Blacquiere M AD - Donald R. Branch, BS, MT(ASCP)SBB, PhD Donald R. Branch, BS, MT(ASCP)SBB, PhD 30 Bond Street, Keenan Research Centre Toronto M5B 1W8 Canada. FAU - Spirig, Rolf AU - Spirig R AD - Research, CSL Biologics Research Center CSL Behring AG Wankdorfstrasse 10 Bern 3010 Switzerland. FAU - Kasermann, Fabian AU - Kasermann F AUID- ORCID: 0000-0002-4255-9350 AD - Research, CSL Biologics Research Center CSL Behring AG Wankdorfstrasse 10 Bern 3010 Switzerland. FAU - Branch, Donald R AU - Branch DR AUID- ORCID: 0000-0002-8974-2451 AD - Donald R. Branch, BS, MT(ASCP)SBB, PhD Donald R. Branch, BS, MT(ASCP)SBB, PhD 30 Bond Street, Keenan Research Centre Toronto M5B 1W8 Canada. AD - Department of Medicine University of Toronto Toronto Canada. LA - eng PT - Journal Article DEP - 20210929 PL - United States TA - EJHaem JT - EJHaem JID - 101761942 PMC - PMC9175896 OTO - NOTNLM OT - ITP OT - ITP intravenous immunoglobulin OT - IVIG OT - IVIg OT - immune thrombocytopenia OT - immunotherapy OT - recombinant Fc hexamer EDAT- 2022/07/19 06:00 MHDA- 2022/07/19 06:01 PMCR- 2021/09/29 CRDT- 2022/07/18 03:47 PHST- 2021/08/10 00:00 [received] PHST- 2021/09/06 00:00 [revised] PHST- 2021/09/09 00:00 [accepted] PHST- 2022/07/18 03:47 [entrez] PHST- 2022/07/19 06:00 [pubmed] PHST- 2022/07/19 06:01 [medline] PHST- 2021/09/29 00:00 [pmc-release] AID - JHA2304 [pii] AID - 10.1002/jha2.304 [doi] PST - epublish SO - EJHaem. 2021 Sep 29;2(4):789-793. doi: 10.1002/jha2.304. eCollection 2021 Nov.