For a long time, IgG has been the only class of antibodies that are actively transferred from mother to offspring. This results in short-term passive immunity, and the specific IgG transport is accomplished by FcRn. In 1972, Jones et.al. first identified a receptor that transport maternal IgG to newborns in the gut of neonatal rats, hence after it was named as Neonatal Fc receptor (FcRn). FcRn expression during pregnancy and lactation plays a role in transporting IgG across the placental barrier and the intestinal tract. A variety of tissue cells can be detected throughout the life cycle. The main function is to maintain the level of IgG and albumin in the serum and regulate the distribution in the tissue.
Human FcRn interaction with ligands IgG and albumin
FcRn is a heterodimer composed of two subunits, FCGRT and B2M. FCGRT has three extracellular functional regions including three soluble domains (α1, α2, and α3), a single transmembrane helix and a cytoplasmic tail (some studies showed the cytoplasmic tail region composed of 44 amino acid residues that may contain signals that mediate intracellular pathways). Its molecular weight is 40 to 50 kDa, called the α chain while the molecular weight of B2M is 14 kDa, called the β chain. The two chains are joining in the form of non-covalent bonds. FCGRT must be assembled with B2M to play a transport role. Studies have shown that the binding site of FcRn with IgG and serum albumin is not the same, so the binding of FcRn to IgG is not interfered by serum albumin.
IgG has a half-life of up to 2 to 4 weeks in the human body. The impact of the half-life is mainly due to the FcRn-mediated recycling mechanism. This mechanism is achieved by the pH-dependent binding of IgG Fc fragment and serum albumin to FcRn.
Under acidic conditions (pH6.0-6.5), FcRn binds IgG, and dissociation occurs under neutral and weakly alkaline conditions (pH7.0-7.5). Specifically, endothelial cells form endocytosis vesicles by ingesting IgG to form an acidified endosome, and IgG binds to FcRn to form an IgG-FcRn complex. The IgG-FcRn complex is transported to the cell surface through the recirculated endosome. Under physiological conditions such as pH7.4, the IgG-FcRn complex is dissociates, and the IgG is released again into the blood circulation. Through this receptor-mediated recycling mechanism, FcRn effectively protects IgG from lysosomal degradation, thus prolonging the half-life of IgG. However, IgG does not bind to FcRn to form an IgG-FcRn complex in the acidified body, degrades in the lysosome. Studies have shown that the FcRn-mediated IgG recovery rate is 42% higher than the IgG production rate, suggesting that IgG recycling is the main process that maintains IgG concentrations in human body.
FcRn-mediated IgG and serum albumin recycling
In addition to half-life evaluation, FcRn has great potential as a therapeutic target. The high affinity of FcRn has harmful effects on IgG-mediated autoimmune diseases such as myasthenia gravis, rheumatoid arthritis, or pemphigus vulgaris. Targeting FcRn and inhibiting FcRn circulation can enhance IgG catabolism, resulting in overall reduced IgG and pathogenic autoantibody levels, which is expected to reduce all autoimmune abnormalities caused by IgG. Studies have confirmed that FcRn targeting therapy provides faster and more selective IgG reduction than therapeutic plasma exchange therapy for myasthenia gravis. In addition, the advantages of this treatment over many clinically use conventional therapies are also demonstrated by the fact that IgA, IgD, IgE, and IgM are not dependent on FcRn-mediated circulation. Therefore, it does not lead to extensive immunosuppression, providing the basis for the safety and precision specificity of FcRn targeting.
Therefore, drugs that target FcRn do not use FcRn as a direct target for therapeutic intervention as conventional targets. Instead, it uses the advantages of cellular drug delivery, which is called a "revolutionary therapy" that can wipe out all autoimmune diseases, with high potential.
To support monoclonal antibody, bispecific antibody, ADC drug affinity research and targeted FcRn drug development for the treatment of autoimmune diseases, ACROBiosystems is providing you with a series of high-quality FcRn proteins.
Expressed by HEK293 Cells: to realize post-translational glycosylation and other modifications and correct protein folding
Various species: Human, Mouse, Cynomolgus/Rhesus macaque, Rat, Porcine, Rabbit, Feline, Bovine, can be fully applied to different cross species experiments
more than 95% as verified by SDS-PAGE
more than 90% as verified by SEC-MALS
Low endotoxin:＜1.0 EU/µg
Biotinylated FcRn proteins labeled with AvitagTM offered. The labeling efficiency is high, and the labeling site is specific and clear, which is suitable for ELISA/SPR/BLI detection based on binding to streptavidin in the process of drug development and process optimization
Affinity verified by SPR & BLI: high-bioactivity guaranteed, and protocols offered free of charge
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The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. The Journal of Clinical Inveatigation. 1972, 51:2916–27.
FcRn: the neonatal Fc receptor comes of age. Nature Reviews Immunology. 2007,7:715–725.
FcRn expression in cancer: Mechanistic basis and therapeutic opportunities. Journal of Controlled Release. 2021, 337 :248–257.
Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis. Frontiers in Immunology. 2020, 10.