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Comparative Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Young animals that suckle soon after birth take colostrum into their intestine. In these young animals, the level of protease activity in the intestine is low, and is further reduced by trypsin inhibitors in colostrum. As a result, colostral proteins are not used as a food source but instead reach the small intestine intact. Colostral IgG then binds to specialized Fc receptors on the intestinal epithelial cells of newborns (FcRn). This receptor is a MHC class lb heterodimer containing a large α chain and β2-microglobulin. Once bound to FcRn, IgG is actively taken up by epithelial cells through pinocytosis and passed through these cells into the bloodstream. Newborn animals thus obtain a transfusion of maternal immunoglobulin.
Antibody-based Radionuclide Imaging
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Steffie M.B. Peters, Erik H. J. G. Aarntzen, Sandra Heskamp
In order to accurately interpret PET/SPECT scans of patients administered with radiolabelled antibodies, it is essential to understand the in vivo behaviour of antibodies. Also, it is important to understand the in vivo fate of the radionuclide in case the antibody is catabolized or the radionuclide becomes detached from the antibody. The latter will be discussed in section 18.4.1. For molecular imaging, radiolabelled antibodies are generally administered intravenously, resulting in rapid systemic distribution via the bloodstream. Circulating radiolabelled antibodies are taken up by different cells followed by degradation or recycling. Radiolabelled antibodies can be rescued from intracellular catabolism through their interaction with the neonatal Fc-receptor (FcRn), which is expressed by endothelial cells lining blood vessels, hepatocytes, and several immune cells such as macrophages, monocytes, and dendritic cells [21, 22]. By binding to FcRn, the antibody is protected from lysosomal degradation, and it is released back in the extracellular space or blood stream. This is the key mechanism responsible for the long serum-half-life of radiolabelled antibodies [21, 23].
Pregnancy-Related Proteins Detected by Their Biological Activities
Published in Gábor N. Than, Hans Bohn, Dénes G. Szabó, Advances in Pregnancy-Related Protein Research, 2020
The IgG (Fcγ) receptor is responsible for the active transport of immunoglobulins G (IgG) from the mother to the fetus across the placenta. The receptor specifically binds the Fc region of IgG. Immunoglobulins of the IgA and IgM type therefore do not pass the placenta. IgG receptors are present on trophoblast plasma membrane as well as on the plasma membrane of other placental cells.
Antigen physiochemical properties allosterically effect the IgG Fc-region and Fc neonatal receptor affinity
Published in mAbs, 2020
Yue Sun, Alberto Estevez, Tilman Schlothauer, Aaron T. Wecksler
FcRn is a major histocompatibility complex (MHC) class I-related heterodimeric Fc receptor, best known for regulating the homeostasis of IgGs.12,13 Binding to FcRn facilitates protection of monomeric IgGs from intracellular degradation and therefore prolongs its serum half-life.14–16 As indicated, the biological role of FcRn on antigen-free IgG recycling has been well established; however, the molecular mechanism of FcRn on antigen-bound IgG (Ag-IgG) trafficking is not as well understood. It has been shown that FcRn can transport Ag-IgG complexes across epithelial cells and FcRn enhances antigen presentation (reviewed in Ref.17). In addition, FcRn-mediated “antibody buffering” can result in prolonged half-life of Ag-IgG from recycling or transcytosis, leading to novel mAb therapeutic strategies for pH-dependent antigen release.18–20 Surprisingly, however, there is little information on the structure-function relationship within the Ag-IgG-FcRn ternary complex, or how the physiochemical properties of the antigen may affect FcRn affinity.
Bioequivalence studies with anti-TNF biosimilars
Published in Expert Opinion on Biological Therapy, 2019
Mercedes Gimeno-Gracia, Carla J. Gargallo-Puyuelo, Fernando Gomollón
Nonclinical studies included a series of in vitro and in vivo studies to demonstrate PD and PK and immunogenic similarities. Similar PK parameters were observed (rat and mice studies). PD studies supported biosimilarity between SB2 and Remicade® as all results were within the similarity range, with the exception of FcγRIIIa (V/V type), FcγRIIb, and FcRn binding assays. However, the difference was within assay variability for FcγRIIb and FcRn binding assays, and binding activity differences in FcγRIIIa (V/V type) and FcγRIIb were not translated into ADCC activity since the ADCC activity of SB2 was within the similarity range. FcRn is known to internalize antibodies into cellular endosomes to protect antibodies from proteolysis and thus plays a role in prolonging half-life of serum IgG. Nevertheless, despite the small deviations outside the similarity margin in FcRn binding activity, these were not translated into PK differences [17,18,20].
Current and emerging treatments for immune thrombocytopenia
Published in Expert Review of Hematology, 2019
The neonatal Fc Receptor (FcRn) is a member of the MHC class I family molecule composed of an α-chain and a β2-microglobulin chain. It is expressed by many cell types such as vascular endothelium, most epithelial cell types, hematopoietic cells including monocytes, neutrophils, macrophages, dendritic cells, and B cells [62]. It plays a major role in the maintenance of plasma IgG and albumin levels, as well as antigen presentation or phagocytosis. IgG endocytosed into the lysosomal compartment can be transported by FcRn to the cell surface and released into plasma, so that IgG can escape from the lysosome and have a long serum half-life [63]. Inhibition of FcRn may reduce the recycle of pathogenic IgG in autoimmune diseases, such as ITP. Therefore, monoclonal antibodies against FcRn have been developed.