ArticleMolecular & cellular proteomics : MCP2017
A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life.
Article in Molecular & cellular proteomics : MCP, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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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
28 citing papers in PubMed, 48 citations in OpenAlex.
- Effectiveness and safety of efgartigimod in patients with anti-NMDAR or anti-LGI1 encephalitis and itsNeuroprotection (Chichester, England) · 2026Article
- Olink Proteomics Analysis Reveals Heterogeneous Responses to FcRn Blockade in Anti-AChR Antibody-Positive Myasthenia Gravis: FGF-19 as a Novel Biomarker.Annals of clinical and translational neurology · 2026Article
- Integrative structural insights into the IgG-FcRn interactions revealed by engineered FcRn-immobilized affinity chromatography.Communications biology · 2026Article
- Impact of timing of a second colostrum feeding on serum immunoglobulin G dynamics in calves during the first week of life.JDS communications · 2026Article
- Identification of a direct interaction between the Fab domains of IgG antibodies and human FcRn upon IgG-FcRn complex formation.Communications biology · 2025Article
- Crossing the Blood-Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies.Pharmaceutics · 2025Review
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Efgartigimod combined with rituximab helps improve the symptoms and reduce the use of corticosteroids in patients with MuSK antibody-positive MG: a single case report.Frontiers in immunology · 2025Article
- Immunomodulation of Antibody Glycosylation through the Placental Transfer.International journal of molecular sciences · 2023Review
- Improving the efficacy of plant-made anti-HIV monoclonal antibodies for clinical use.Frontiers in plant science · 2023Article
- Physiologically-based pharmacokinetic model for pulmonary disposition of protein therapeutics in humans.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life.Communications biology · 2022Article
- A homogeneous bioluminescent immunoassay for parallel characterization of binding between a panel of antibodies and a family of Fcγ receptors.Scientific reports · 2022Article
- Antibody variable sequences have a pronounced effect on cellular transport and plasma half-life.iScience · 2022Article
- Stepping forward in antibody-drug conjugate development.Pharmacology & therapeutics · 2022Review
- Bispecific Antibodies for IFN-β Delivery to ErbB2Biomolecules · 2021Article
- Deciphering the Interaction between Neonatal Fc Receptor and Antibodies Using a Homogeneous Bioluminescent Immunoassay.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Highly sensitive HPLC analysis and biophysical characterization of N-glycans of IgG-Fc domain in comparison between CHO and 293 cells using FcγRIIIa ligand.Biotechnology progress · 2020Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH-dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively. Some IgGs, like the antibody briakinumab has an unusually short half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct FcRn interactions with both the Fc region and the Fab regions of briakinumab, and correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction.
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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.