A monoclonal antibody with anti-D-like activity in murine immune thrombocytopenia requires Fc domain function for immune thrombocytopenia ameliorative effects

Transfusion
Xiaojie YuAlan H Lazarus

Abstract

The mechanism of action of anti-D in ameliorating immune thrombocytopenia (ITP) remains unclear. The monoclonal antibody (MoAb) Ter119, which targets murine red blood cells (RBCs), has been shown to mimic the effect of anti-D in improving antibody-mediated murine ITP. The mechanism of Ter119-mediated ITP amelioration, especially the role of the antigen-binding and Fc domains, remains untested. A functional Fc domain is crucial for many therapeutic MoAb activity; therefore, the requirement of Ter119 Fc domain in ITP amelioration is investigated using outbred CD-1 mice. Ter119 variants, including Ter119 F(ab')2 fragments, deglycosylated Ter119, and afucosylated Ter119, were generated to test their effect in ameliorating antibody-induced murine ITP. In vivo inhibition of FcγRIII and FcγRIIB was achieved using the Fab fragment of the FcγRIII/FcγRIIB-specific MoAb 2.4G2. Ter119 F(ab')2 fragments and deglycosylated Ter119 were unable to ameliorate murine ITP or mediate phagocytosis of RBCs by RAW264.7 macrophages in vitro. Inhibition of FcγRIII and FcγRIIB, as well as Ter119 defucosylation, do not affect Ter119-mediated ITP amelioration. The Fc domain of Ter119, as well as its Fc glycosylation, is required for Ter119-mediated ITP ame...Continue Reading

References

Mar 13, 2001·Annual Review of Immunology·J V Ravetch, S Bolland
Dec 31, 2002·Archives of Medical Research·Raúl Ambriz-FernándezJavier Bautista-Juárez
May 3, 2003·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Alan H Lazarus, Andrew R Crow
May 21, 2005·Biotechnology Progress·Royston Jefferis
Jul 26, 2005·Immunity·Falk NimmerjahnJeffrey V Ravetch
Dec 3, 2005·Science·Falk Nimmerjahn, Jeffrey V Ravetch
Jan 18, 2006·Immunity·Falk Nimmerjahn, Jeffrey V Ravetch
Oct 13, 2006·Annual Review of Immunology·James N ArnoldRaymond A Dwek
Dec 8, 2007·Nature Reviews. Immunology·Falk Nimmerjahn, Jeffrey V Ravetch
Nov 26, 2009·Hematology/oncology Clinics of North America·Nichola Cooper
Jul 8, 2010·The Journal of Pharmacology and Experimental Therapeutics·Ronald HerbstAnthony J Coyle
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Claudia FerraraJörg Benz
Oct 3, 2012·Journal of the American Chemical Society·Thomas A BowdenMax Crispin
Mar 20, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anja LuxFalk Nimmerjahn
Jun 12, 2013·Journal of the American Chemical Society·Xiaojie YuMax Crispin
Aug 8, 2013·Analytical Chemistry·Henning StöckmannPauline M Rudd
Aug 8, 2013·Expert Opinion on Biological Therapy·Alan H Lazarus
Oct 22, 2013·The Journal of Allergy and Clinical Immunology·Marat V KhodounFred D Finkelman
Jan 10, 2014·The New England Journal of Medicine·Valentin GoedeMichael Hallek

❮ Previous
Next ❯

Citations

Feb 9, 2016·Autoimmunity Reviews·Xiaojie Yu, Alan H Lazarus
Jan 20, 2018·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Nikhil MistryGregory M T Hare
Aug 23, 2019·Science Translational Medicine·Andrew R CrowAlan H Lazarus
Mar 18, 2021·Autoimmunity Reviews·Xing ZhouWeici Zhang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.