Evidence map›Paper›PMID 40311815›Full record

ArticleThe Journal of allergy and clinical immunology2025

Fine resolution of the N-terminal IgE-binding epitope of Ara h 2: Discovery of variants with enhanced IgE binding.

Joshua S Bernstein, Nicole Canon, Catherine H Schein, Werner Braun, Surendra S Negi, Raffi Tchekmedyian, Marina Pozzoli, Edwin H Kim, Michael D Kulis, Thao Vu and 3 more

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Article in The Journal of allergy and clinical immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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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

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Joshua S BernsteinDivision of Allergy, Department of Medicine, University of Cincinnati, Cincinnati, Ohio.
Nicole CanonDepartment of Allergy, Kaiser Permanente Northern California, Vacaville, Calif.
Catherine H ScheinInstitute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Tex; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Tex; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Tex.
Werner BraunSealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Tex; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Tex.
Surendra S NegiSealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Tex; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Tex.
Raffi TchekmedyianModena Allergy and Asthma, Torrance, Calif.
Marina PozzoliDepartment of Ophthalmology, University of Colorado Denver, Denver, Colo.
Edwin H KimDivision of Pediatric Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.
Michael D KulisDivision of Pediatric Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC.
Thao VuDepartment of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colo.
Weimin LiuDivision of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colo.
Xueni ChenDivision of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colo.
Stephen C DreskinDivision of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colo. Electronic address: stephen.dreskin@cuanschutz.edu.

Funding

Exploiting and enhancing IgE-binding epitopes of the 2S albumins of peanuts and tree nutsR01AI165866 · NIAID · UNIVERSITY OF COLORADO DENVER · PI STEPHEN C DRESKIN · 2021 to 2026
$4.2M
Prediction and Classification of Allergenicity in a Protein FamilyR21AI109090 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BRAUN, WERNER A · 2014 to 2015
$440k
Designing peptides to block Ara h 2 and Ara h 6 from binding to IgER21AI135397 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DRESKIN, STEPHEN C · 2019 to 2020
$427k
NIAID NIH HHS R01 AI165866NIAID NIH HHS R21 AI109090NIAID NIH HHS R21 AI135397
6 · The paper itself

Abstract

backgroundIgE binding to linear peptides from the N-terminal region of Ara h 2 (epitope 1) is associated with the achievement of sustained unresponsiveness in young children receiving oral immunotherapy and may be important for cross-reactivity between peanuts and tree nuts. This region is also part of the binding site for neutralizing IgG monoclonal antibodies associated with sustained unresponsiveness following oral immunotherapy.

objectiveWe sought to perform alanine scanning of this epitope to determine the importance of individual amino acids and then amino acid scanning to screen for sequences with enhanced binding of IgE.

methodsA streptavidin IgE ELISA with biotinylated peptides was used to measure the binding of IgE to full-length and truncated peptides to identify a core sequence (DRRCQSQLERAN, amino acids 30-41 in the Ara h 2 sequence). Peptide microarrays were used to screen multiple peptides and quantitate binding of IgE. Statistical analysis included one-way ANOVA followed by the Dunnett multiple comparison test.

resultsIgE binding was greatly reduced when alanine was substituted for arginine at positions 31, 32, and 39 (R31, P < .001; R32, P < .01; R39, P < .001); glutamine at positions 34 and 36 (Q34, P < .01; Q36, P < .001); and glutamate at position 38 (E38, P < .01). Substitution of aspartate with asparagine at position D30 in conjunction with substitution of asparagine at position N41 with either leucine or lysine gave enhanced binding (P < .0001). Molecular modeling of these data suggests a conformational basis for recognition by polyclonal IgE.

conclusionsIgE binding assays using pooled and individual sera demonstrated the importance of amino acids throughout the sequence of epitope 1 for immune recognition. The results of alanine scanning indicated residues that could be changed as part of a larger strategy to generate hypoallergenic forms of Ara h 2, whereas sequence variants with enhanced binding were identified that may be useful for improving diagnostics.

Indexed as

2S Albumins, PlantAntigens, PlantEpitopesImmunoglobulin EAmino Acid SequenceEpitope MappingHumansPeanut HypersensitivityPeptidesProtein Binding2S Albumins, PlantAntigens, PlantAra h 2 allergen, Arachis hypogaeaEpitopesImmunoglobulin EPeptides2S albuminsAra h 2epitopefood allergyIgEmimotopepeanutspeptides

Identifiers

PMID40311815
PMCPMC12278769

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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.