ArticleThe Journal of allergy and clinical immunology2021
Structure-guided design of ultrapotent disruptive IgE inhibitors to rapidly terminate acute allergic reactions.
Article in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Safety of inactivated SARS-CoV-2 vaccines in patients with allergic diseases.Respiratory research · 2022Trial
- IgE and non-IgE-mediated pathways in anaphylaxis.Seminars in immunopathology · 2025Review
- Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition.Immunological reviews · 2025Review
- Emerging diagnostic and therapeutic opportunities in food allergy.Frontiers in immunology · 2025Review
- Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways.Immunological reviews · 2024Review
- Allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of IgE F(ab')2 epitopes.Communications biology · 2024Article
- Management of Refractory Anaphylaxis: An Overview of Current Guidelines.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2024Review
- Comparative analyses of various IgE-mediated and non-IgE-mediated inducers of mast cell degranulation for in vitro study.Immunologic research · 2024Article
- Case Report: A Rare Case of Iodixanol-Induced Anaphylactic Shock in Cerebral Angiography.Journal of asthma and allergy · 2024Article
- Mast cell stabilizers: from pathogenic roles to targeting therapies.Frontiers in immunology · 2024Review
- Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy.The Journal of allergy and clinical immunology · 2024Article
- Research Advances in Mast Cell Biology and Their Translation Into Novel Therapies for Anaphylaxis.The journal of allergy and clinical immunology. In practice · 2023Review
- Treatment of food allergy: Oral immunotherapy, biologics, and beyond.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2023Review
- New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis.Clinical science (London, England : 1979) · 2023Review
- The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders.The Journal of allergy and clinical immunology · 2023Review
- Peanut allergen inhibition prevents anaphylaxis in a humanized mouse model.Science translational medicine · 2023Article
- New Mechanistic Advances in FcεRI-Mast Cell-Mediated Allergic Signaling.Clinical reviews in allergy & immunology · 2022Review
- Review
- Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation.International journal of molecular sciences · 2022Review
- Biologics as novel therapeutics for the treatment of allergy: Challenges and opportunities.Frontiers in allergy · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAnaphylaxis represents one of the most severe and fatal forms of allergic reactions. Like most other allergies, it is caused by activation of basophils and mast cells by allergen-mediated cross-linking of IgE bound to its high-affinity receptor, FcεRI, on the cell surface. The systemic release of soluble mediators induces an inflammatory cascade, rapidly causing symptoms with peak severity in minutes to hours after allergen exposure. Primary treatment for anaphylaxis consists of immediate intramuscular administration of adrenaline.
objectiveWhile adrenaline alleviates life-threatening symptoms of an anaphylactic reaction, there are currently no disease-modifying interventions available. We sought to develop potent and fast-acting IgE inhibitors with the potential to rapidly terminate acute allergic reactions.
methodsUsing affinity maturation by yeast display and structure-guided molecular engineering, we generated 3 optimized disruptive IgE inhibitors based on designed ankyrin repeat proteins and assessed their ability to actively remove IgE from allergic effector cells in vitro as well as in vivo in mice.
resultsThe engineered IgE inhibitors rapidly dissociate preformed IgE:FcεRI complexes, terminate IgE-mediated signaling in preactivated human blood basophils in vitro, and shut down preinitiated allergic reactions and anaphylaxis in mice in vivo.
conclusionsFast-acting disruptive IgE inhibitors demonstrate the feasibility of developing kinetically optimized inhibitors for the treatment of anaphylaxis and the rapid desensitization of allergic individuals.
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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.