ArticlePharmaceutical research2018
First Infusion Reactions are Mediated by FcγRIIIb and Neutrophils.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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.
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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
8 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Bridging pharmacovigilance and genetic insight: investigating drugs and indications for breast cancer risk in women with autoimmune diseases.Journal of translational medicine · 2025Article
- Regulatory considerations in the design, development and quality of monoclonal antibodies and related products for the diagnosis and treatment of cancer.Frontiers in oncology · 2024Review
- Potential Target Genes in the Development of Atrial Fibrillation: A Comprehensive Bioinformatics Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Acute and Chronic Dosing of a High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody in Mice.Pharmaceutics · 2020Article
- Exploration and Evaluation of Therapeutic Efficacy of Drug-Free Macromolecular Therapeutics in Collagen-Induced Rheumatoid Arthritis Mouse Model.Macromolecular bioscience · 2020Article
- The Binding of Human IgG to Minipig FcγRs - Implications for Preclinical Assessment of Therapeutic Antibodies.Pharmaceutical research · 2019Article
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAdministration of therapeutic monoclonal antibodies (mAbs) is frequently accompanied by severe first infusion reactions (FIR). The mechanism driving FIR is still unclear. This study aimed to investigate the cellular and molecular mechanisms causing FIR in humanized mouse models and their potential for evaluating FIR risk in patients.
methodsMice humanized for Fc gamma receptors (FcγRs) were generated by recombination-mediated genomic replacement. Body temperature, cytokine release and reactive oxygen species (ROS) were measured to assess FIR to mAbs.
resultsInfusion of human mAb specific for mouse transferrin receptor (HamTfR) into FcγR-humanized mice, produced marked transient hypothermia accompanied by an increase in inflammatory cytokines KC and MIP-2, and ROS. FIR were dependent on administration route and Fc-triggered effector functions mediated by neutrophils. Human neutrophils also induced FIR in wild type mice infused with HamTfR. Specific knock-in mice demonstrated that human FcγRIIIb on neutrophils was both necessary and sufficient to cause FIR. FcγRIIIb-mediated FIR was abolished by depleting neutrophils or blocking FcγRIIIb with CD11b antibodies.
conclusionsHuman FcγRIIIb and neutrophils are primarily responsible for triggering FIR. Clinical strategies to prevent FIR in patients should focus on this pathway and may include transient depletion of neutrophils or blocking FcγRIIIb with specific mAbs.
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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.