ArticleNature communications2022
The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Trial
- Structure-function analysis of the FCRL5-IgG1 Fc complex reveals an unappreciated pathway for B cell modulation by Fc-attenuated IgG.Science advances · 2026Article
- Ontogeny of Placental FcRn Protein During Human and Animal Pregnancy to Inform Developmental Toxicity Testing.Birth defects research · 2026Article
- Structure-Function Analysis of the FCRL5-IgG1 Fc Complex Reveals an Unappreciated Effect of Fc-Silent Antibodies on B cells.bioRxiv : the preprint server for biology · 2026Article
- The conserved human astrovirus-receptor interface reveals a targetable vulnerability for antiviral development.Nature communications · 2026Article
- Integrative structural insights into the IgG-FcRn interactions revealed by engineered FcRn-immobilized affinity chromatography.Communications biology · 2026Article
- Ozoralizumab, a trivalent anti-TNFα NANOBODYFrontiers in immunology · 2026Article
- The Impact of Cognate Antigen Binding on the FcRn-mediated Transcytosis and Recycling of Monoclonal Antibodies.The AAPS journal · 2025Article
- Article
- Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties.mAbs · 2025Article
- Review
- Effects and mechanisms of monoclonal and polyclonal human antibodies in protection of humanized mice from HIV-1 challenge.bioRxiv : the preprint server for biology · 2025Article
- Technological advancements in antibody-based therapeutics for treatment of diseases.Journal of biomedical science · 2025Review
- The mechanistic basis for interprotomer deglycosylation of antibodies by corynebacterial IgG-specific endoglycosidases.Nature communications · 2025Article
- Interrogation of Structure-Activity Relationships in Charge Variants of Therapeutic IgG2s Enabled by Free-Flow Isoelectric Focusing Fractionation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Article
- Identification of a direct interaction between the Fab domains of IgG antibodies and human FcRn upon IgG-FcRn complex formation.Communications biology · 2025Article
- Enhanced plasma half-life and efficacy of engineered human albumin-fused GLP-1 despite enzymatic cleavage of its C-terminal end.Communications biology · 2025Article
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Engineering FcRn binding kinetics dramatically extends antibody serum half-life and enhances therapeutic potential.Journal of biological engineering · 2025Article
- SynBioNanoDesign: pioneering targeted drug delivery with engineered nanomaterials.Journal of nanobiotechnology · 2025Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Binding to the neonatal Fc receptor (FcRn) extends serum half-life of IgG, and antagonizing this interaction is a promising therapeutic approach in IgG-mediated autoimmune diseases. Fc-MST-HN, designed for enhanced FcRn binding capacity, has not been evaluated in the context of a full-length antibody, and the structural properties of the attached Fab regions might affect the FcRn-mediated intracellular trafficking pathway. Here we present a comprehensive comparative analysis of the IgG salvage pathway between two full-size IgG1 variants, containing wild type and MST-HN Fc fragments, and their Fc-only counterparts. We find no evidence of Fab-regions affecting FcRn binding in cell-free assays, however, cellular assays show impaired binding of full-size IgG to FcRn, which translates into improved intracellular FcRn occupancy and intracellular accumulation of Fc-MST-HN compared to full size IgG1-MST-HN. The crystal structure of Fc-MST-HN in complex with FcRn provides a plausible explanation why the Fab disrupts the interaction only in the context of membrane-associated FcRn. Importantly, we find that Fc-MST-HN outperforms full-size IgG1-MST-HN in reducing IgG levels in cynomolgus monkeys. Collectively, our findings identify the cellular membrane context as a critical factor in FcRn biology and therapeutic targeting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.