Evidence map›Paper›PMID 24642143›Full record

ArticleThe Journal of allergy and clinical immunology2014

Accelerated dissociation of IgE-FcεRI complexes by disruptive inhibitors actively desensitizes allergic effector cells.

Alexander Eggel, Günther Baravalle, Gabriel Hobi, Beomkyu Kim, Patrick Buschor, Patrik Forrer, Jeoung-Sook Shin, Monique Vogel, Beda M Stadler, Clemens A Dahinden and 1 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 150 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Developments in Mast Cell Research.The Journal of allergy and clinical immunology · 2026
    Review
  4. Review
  5. Emerging Therapies for Anaphylaxis.Immunology and allergy clinics of North America · 2026
    Review
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  17. Article
  18. Treatment of food allergy: Oral immunotherapy, biologics, and beyond.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2023
    Review
  19. Research Advances in Mast Cell Biology and Their Translation Into Novel Therapies for Anaphylaxis.The journal of allergy and clinical immunology. In practice · 2023
    Review
  20. Review

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Alexander EggelInstitute of Immunology, University of Bern, Bern, Switzerland. Electronic address: alexander.eggel@iib.unibe.ch.
Günther BaravalleDepartment of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, Calif.
Gabriel HobiInstitute of Immunology, University of Bern, Bern, Switzerland.
Beomkyu KimDepartment of Structural Biology, Stanford University School of Medicine, Stanford, Calif.
Patrick BuschorInstitute of Immunology, University of Bern, Bern, Switzerland.
Patrik ForrerMolecular Partners AG, Zürich-Schlieren, Switzerland.
Jeoung-Sook ShinDepartment of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, Calif.
Monique VogelInstitute of Immunology, University of Bern, Bern, Switzerland.
Beda M StadlerInstitute of Immunology, University of Bern, Bern, Switzerland.
Clemens A DahindenInstitute of Immunology, University of Bern, Bern, Switzerland.
Theodore S JardetzkyDepartment of Structural Biology, Stanford University School of Medicine, Stanford, Calif.
University of Bern · CHStanford University · USUniversity of California, San Francisco · USMolecular Partners (Switzerland) · CH

Funding

Structural Studies of IgE ReceptorsR37AI038972 · NIAID · STANFORD UNIVERSITY · PI JARDETZKY, THEODORE S · 2001 to 2010
$3.0M
Structural Studies of IgE ReceptorsR56AI038972 · NIAID · STANFORD UNIVERSITY · PI JARDETZKY, THEODORE S · 2014 to 2014
$400k
SPECIFICITY OF INDIVIDUAL HELPER T LYMPHOCYTESR01AI018939 · NIAID · NORTHWESTERN UNIVERSITY · PI PIERCE, SUSAN K. · 1985 to 1989
–
SPECIFICITY OF INDIVIDUAL HELPER T LYMPHOCYTESR37AI018939 · NIAID · NORTHWESTERN UNIVERSITY · PI PIERCE, SUSAN K. · 1990 to 1999
–
NIAID NIH HHS AI-18939NIAID NIH HHS R37 AI038972NIAID NIH HHS R56 AI038972
6 · The paper itself

Abstract

backgroundThe remarkably stable interaction of IgE with its high-affinity receptor FcεRI on basophils and mast cells is critical for the induction of allergic hypersensitivity reactions. Because of the exceptionally slow dissociation rate of IgE-FcεRI complexes, such allergic effector cells permanently display allergen-specific IgE on their surface and immediately respond to allergen challenge by releasing inflammatory mediators. We have recently described a novel macromolecular inhibitor that actively promotes the dissociation of IgE from FcεRI through a molecular mechanism termed facilitated dissociation.

objectiveHere we assessed the therapeutic potential of this non-immunoglobulin-based IgE inhibitor E2_79, a designed ankyrin repeat protein (DARPin), as well as a novel engineered biparatopic DARPin bi53_79, and directly compared them with the established anti-IgE antibody omalizumab.

methodsIgE-FcεRI complex dissociation was analyzed in vitro by using recombinant proteins in ELISA and surface plasmon resonance, ex vivo by using human primary basophils with flow cytometry, and in vivo by using human FcεRI α-chain transgenic mice in a functional passive cutaneous anaphylaxis test.

resultsWe show that E2_79-mediated removal of IgE from primary human basophils fully abrogates IgE-dependent cell activation and release of proinflammatory mediators ex vivo. Furthermore, we report that omalizumab also accelerates the dissociation of IgE from FcεRI, although much less efficiently than E2_79. Using the biparatopic IgE targeting approach, we further improved the disruptive potency of E2_79 by approximately 100-fold and show that disruptive IgE inhibitors efficiently prevent passive cutaneous anaphylaxis in mice expressing the human FcεRI α-chain.

conclusionOur findings highlight the potential of such novel IgE inhibitors as important diagnostic and therapeutic tools for management of allergic diseases.

Indexed as

Ankyrin RepeatAnaphylaxisAnimalsAntibodies, Anti-IdiotypicAntibodies, Monoclonal, HumanizedAntigensBasophilsDose-Response Relationship, DrugHumansImmunoglobulin EMast CellsMiceMice, TransgenicModels, MolecularMolecular MimicryOmalizumabAntibodies, Anti-IdiotypicAntibodies, Monoclonal, HumanizedAntigensanti-IgE antibodiesDARPin E2 79Immunoglobulin EOmalizumabReceptors, IgERecombinant Fusion ProteinsAllergybasophilsdesigned ankyrin repeat proteinsFcεRIαIgEinhibitorsmast cells

Identifiers

PMID24642143
PMCPMC4083100
OpenAlexW2085071459

What OpenQuestion holds

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Registered trials

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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.