Differential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin.

Autor:	Ma G; Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Crowley AR; Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Heyndrickx L; argenx, Zwijnaarde, Ghent, Belgium., Rogiers I; argenx, Zwijnaarde, Ghent, Belgium., Parthoens E; VIB BioImaging Core, Center for Inflammation Research, Ghent, Belgium., Van Santbergen J; argenx, Zwijnaarde, Ghent, Belgium., Ober RJ; Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Bobkov V; argenx, Zwijnaarde, Ghent, Belgium., de Haard H; argenx, Zwijnaarde, Ghent, Belgium., Ulrichts P; argenx, Zwijnaarde, Ghent, Belgium., Hofman E; argenx, Zwijnaarde, Ghent, Belgium., Louagie E; argenx, Zwijnaarde, Ghent, Belgium., Balbino B; argenx, Zwijnaarde, Ghent, Belgium., Ward ES; Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 May 07; Vol. 9 (10). Date of Electronic Publication: 2024 May 07.
DOI:	10.1172/jci.insight.176166
Abstrakt:	The homeostasis of IgG is maintained by the neonatal Fc receptor, FcRn. Consequently, antagonism of FcRn to reduce endogenous IgG levels is an emerging strategy for treating antibody-mediated autoimmune disorders using either FcRn-specific antibodies or an engineered Fc fragment. For certain FcRn-specific antibodies, this approach has resulted in reductions in the levels of serum albumin, the other major ligand transported by FcRn. Cellular and molecular analyses of a panel of FcRn antagonists have been carried out to elucidate the mechanisms leading to their differential effects on albumin homeostasis. These analyses have identified 2 processes underlying decreases in albumin levels during FcRn blockade: increased degradation of FcRn and competition between antagonist and albumin for FcRn binding. These findings have potential implications for the design of drugs to modulate FcRn function.
Databáze:	MEDLINE
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