Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform

Deak, Peter E.; Vrabel, Maura R.; Kiziltepe, Tanyel; Bilgiçer, Başar

doi:10.1038/s41598-017-04268-6

Cited by 22 publications

(22 citation statements)

References 42 publications

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“…Our results show that specific peptide reactivity is highly variable between individual patients. A similar observation was reported by Deak et al 47 They developed "nanoallergens", a nanoparticle-based platform for multivalent testing of potential epitopes of Ara h 2 in a cell-based assay. They concluded that some epitopes are more "im-…”

Section: Patient-specific Allergen Recognition Patternssupporting

confidence: 73%

The immunome of soy bean allergy: Comprehensive identification and characterization of epitopes

Kern

Havenith

Delaroque

et al. 2018

Clin Experimental Allergy

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Summary Background The precise mapping of multiple antibody epitopes recognized by patients’ sera allows a more detailed and differentiated understanding of immunological diseases. It may lead to the development of novel therapies and diagnostic tools. Objective Mapping soy bean specific epitopes relevant for soy bean allergy patients and persons sensitized to soy bean, and analysis of their IgE/IgG binding spectrum. Methods Identification of epitopes using sera, applying an optimized peptide phage display library followed by next‐generation sequencing, specially designed in silico data analysis and subsequent peptide microarray analysis. Results We were able to identify more than 400 potential epitope motifs in soy bean proteins. More than 60% of them have not yet been described as potential epitopes. Eighty‐three peptides, representing the 42 most frequently found epitope candidates, were validated by microarray analysis using 50 sera from people who have been tested positive in skin prick test (SPT). Of these peptides, 56 were bound by antibodies, 55 by serum IgE, 43 by serum IgG and 30 by both. Person‐specific epitope patterns were found for each individual and protein. Conclusions For individuals with clinical symptoms, epitope resolved analyses reveal a high prevalence of IgE binding to a few soy bean specific epitopes. Evaluation of individual immune profiles of patients with soy bean sensitization allows the identification of peptides that do facilitate studying individual IgE/IgG epitope binding patterns. This enables discrimination of sensitization from disease, such assay test has the potential to replace SPT assays

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Section: Patient-specific Allergen Recognition Patternssupporting

confidence: 73%

The immunome of soy bean allergy: Comprehensive identification and characterization of epitopes

Kern

Havenith

Delaroque

et al. 2018

Clin Experimental Allergy

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“…Based on their medical history, symptoms of the IgE-mediated peanut allergy involved skin, respiratory tract, gastrointestinal tract, and cardiovascular system. Twelve sera from US peanut-allergic patients with a strong history of peanut-induced immediate hypersensitivity and peanut-specific IgE ≥13 KAU/L (ImmunoCap; Thermo Fischer Scientific) in serum were also included (Table S1, sera [21][22][23][24][25][26][27][28][29][30][31][32]. All adult patients and the parents or guardians of minors signed informed consent.…”

Section: Human Seramentioning

confidence: 99%

“…This absence of distinction is illustrated inFigure 4with nAra h 2 and rAra h 2 displaying similar IgE-binding capacities although the absence of hydroxyproline in rAra h 2 has been shown to reduce the binding affinity of IgE recognizing the DPYSP OH S motifs in nAra h 2. In contrast, assays such as IgE-binding competitive inhibition or in vitro mast cell degranulation can evidence differences of binding affinity and could thus demonstrate the higher allergenic activity of nAra h 2 compared with rAra h 2 22,32. We therefore investigated cross-reactivity between 2S-albumins with a competitive fluidphase assay (Figure 5A).…”

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confidence: 99%

Variable IgE cross‐reactivity between peanut 2S‐albumins: The case for measuring IgE to both Ara h 2 and Ara h 6

Hazebrouck

Guillon

Paty

et al. 2019

Clin Experimental Allergy

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Background: 2S-albumins Ara h 2 and Ara h 6 are the most potent peanut allergens and levels of specific immunoglobulin E (IgE) towards these proteins are good predictors of clinical reactivity. Because of structural homologies, Ara h 6 is generally considered to cross-react extensively with Ara h 2.Objective: We aimed to quantify the IgE cross-reactivity between Ara h 2 and Ara h 6.Methods: Peanut 2S-albumins were purified from raw peanuts. The IgE cross-reactivity between Ara h 2 and Ara h 6 was evaluated with 32 sera from French and US peanut-allergic patients by measuring the residual IgE-binding to one 2S-albumin after depletion of IgE antibodies recognizing the other 2S-albumin. The IgE cross-reactivity between Ara h 2 and Ara h 6 was further investigated by competitive inhibition of IgE-binding and by a model of mast cell degranulation. Results:A highly variable level of IgE cross-reactivity was revealed among the patients. The mean fraction of cross-reactive IgE antibodies represented only 17.1% of 2S-albumins-specific IgE antibodies and was lower than the mean fraction of IgE specific to Ara h 2 (57.4%) or to Ara h 6 (25.5%). The higher level of Ara h 2-specific IgE was principally due to the IgE-binding capacity of an insertion containing the repeated immunodominant linear epitope DPYSP OH S. The impact of IgE cross-reactivity on diagnostic testing was illustrated with a serum displaying an Ara h 6-specific IgE response of 26 UI/mL that was not associated with the capacity of Ara h 6 to trigger mast cell degranulation. Conclusions & Clinical Relevance: Immunoglobulin E antibodies specific to peanut 2S-albumins are mainly non-cross-reactive, but low-affinity cross-reactivity can affect diagnostic accuracy. Testing IgE-binding to a mixture of 2S-albumins rather than to each separately may enhance diagnostic performance. K E Y W O R D S

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“…2 and Ara h 6 using the nanoallergen assay system developed in our laboratory (12). Nanoallergens provide multivalent display for allergen epitopes on liposomal surfaces, which are then used to evaluate their immunogenicity via in vitro mast cell degranulation responses ( Fig.…”

Section: Identification Of Immunodominant Ara H 2 and Ara H 6 Epitopementioning

confidence: 99%

“…S2). These nanoallergens multivalently present epitopes on their surfaces with high-precision and controlled stoichiometry (12,14). Nanoallergens were used to trigger degranulation response in RBL-SX38 cells [model mast cell line which expresses human IgE receptor (FceRI)] (15) primed with a specific patient serum (Fig.…”

Section: Identification Of Immunodominant Ara H 2 and Ara H 6 Epitopementioning

confidence: 99%

Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen

Deak

Kim

Qayum

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Allergies are a result of allergen proteins cross-linking allergen-specific IgE (sIgE) on the surface of mast cells and basophils. The diversity and complexity of allergen epitopes, and high-affinity of the sIgE–allergen interaction have impaired the development of allergen-specific inhibitors of allergic responses. This study presents a design of food allergen-specific sIgE inhibitors named covalent heterobivalent inhibitors (cHBIs) that selectively form covalent bonds to only sIgEs, thereby permanently inhibiting them. Using screening reagents termed nanoallergens, we identified two immunodominant epitopes in peanuts that were common in a population of 16 allergic patients. Two cHBIs designed to inhibit only these two epitopes completely abrogated the allergic response in 14 of the 16 patients in an in vitro assay and inhibited basophil activation in an allergic patient ex vivo analysis. The efficacy of the cHBI design has valuable clinical implications for many allergen-specific responses and more broadly for any antibody-based disease.

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Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform

Cited by 22 publications

References 42 publications

The immunome of soy bean allergy: Comprehensive identification and characterization of epitopes

The immunome of soy bean allergy: Comprehensive identification and characterization of epitopes

Variable IgE cross‐reactivity between peanut 2S‐albumins: The case for measuring IgE to both Ara h 2 and Ara h 6

Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen

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