ArticleThe Journal of biological chemistry2010
Cross-species binding analyses of mouse and human neonatal Fc receptor show dramatic differences in immunoglobulin G and albumin binding.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 196 citations in OpenAlex.
- Phase I/II Trial of a Combination of Anti-CD3/CD7 Immunotoxins for Steroid-Refractory Acute Graft-versus-Host Disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Trial
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- Monovalent Anti-FcγRIIA Antibody Blocks Immune-Mediated Thrombocytopenia and Thrombosis With Minimal Adverse Side Effects in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Re-engineering CD154 blockade for transplantation: Fc-free design to separate thrombotic risk from therapeutic function.Clinical transplantation and research · 2026Review
- Targeted FcRn to deliver epitope-optimized RBD confers broad-spectrum mucosal protection against SARS-CoV-2.Molecular therapy. Nucleic acids · 2026Article
- Humanized mice enableMolecular therapy. Advances · 2026Article
- CSL305: A Dual Functional Therapeutic Antibody Targeting Complement C2 and FcRn.International journal of molecular sciences · 2026Article
- Review
- Review
- Tailored collagen binding of albumin-fused hyperactive coagulation factor IX dictates in vivo distribution and functional properties.Nature communications · 2025Article
- Engineering B cells to treat and study human disease.Nature biotechnology · 2025Review
- Advanced human FcRn knock-in mice for pharmacokinetic profiling of therapeutic antibodies.Scientific reports · 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
- An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models.Nature communications · 2025Article
- Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Plant-derived recombinant macromolecular PAP-IgG Fc as a novel prostate cancer vaccine candidate eliciting robust immune responses.Transgenic research · 2025Article
- Article
- Engineering of anticancer human immunoglobulin A equipped with albumin for enhanced plasma half-life.PNAS nexus · 2025Article
- Podocyte, tubular epithelial-immune cell interplay in the pathogenesis of lupus nephritis.Frontiers in immunology · 2025Review
- Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria.Nature communications · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neonatal Fc receptor (FcRn) regulates the serum half-life of both IgG and albumin through a pH-dependent mechanism that involves salvage from intracellular degradation. Therapeutics and diagnostics built on IgG, Fc, and albumin fusions are frequently evaluated in rodents regarding biodistribution and pharmacokinetics. Thus, it is important to address cross-species ligand reactivity with FcRn, because in vivo testing of such molecules is done in the presence of competing murine ligands, both in wild type (WT) and human FcRn (hFcRn) transgenic mice. Here, binding studies were performed in vitro using enzyme-linked immunosorbent assay and surface plasmon resonance with recombinant soluble forms of human (shFcRn(WT)) and mouse (smFcRn(WT)) receptors. No binding of albumin from either species was observed at physiological pH to either receptor. At acidic pH, a 100-fold difference in binding affinity was observed. Specifically, smFcRn(WT) bound human serum albumin with a K(D) of approximately 90 microM, whereas shFcRn(WT) bound mouse serum albumin with a K(D) of 0.8 microM. shFcRn(WT) ignored mouse IgG1, and smFcRn(WT) bound strongly to human IgG1. The latter pair also interacted at physiological pH with calculated affinity in the micromolar range. In all cases, binding of albumin and IgG from either species to both receptors were additive. Cross-species albumin binding differences could partly be explained by non-conserved amino acids found within the alpha2-domain of the receptor. Such distinct cross-species FcRn binding differences must be taken into consideration when IgG- and albumin-based therapeutics and diagnostics are evaluated in rodents for their pharmacokinetics.
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