biostudies-literatureUnknown9(10)Ma GThe 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 FcRnJCI insighte176166https://www.ebi.ac.uk/biostudies/studies/S-EPMC11141909biostudies-literatureDifferential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin.PMC11141909Crowley ARHofman EBobkov VWard ESde Haard HHeyndrickx LRogiers IVan Santbergen JOber RJLouagie EParthoens EUlrichts PBalbino BMa GfalseDifferential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin.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 FcRn2024-01-01T00:00:00Z2024 May2026-06-02T01:37:30.321Z2026-04-13T03:12:24.934ZS-EPMC111419093871353410.1172/jci.insight.176166