An unfolded variant of the major peanut allergen Ara h 2 with decreased anaphylactic potential

Starkl, Philipp; Felix, Ferdinand; Krishnamurthy, Durga; Stremnitzer, Caroline; Roth‐Walter, Franziska; Prickett, Sara; Voskamp, Astrid; Willensdorfer, Anna; Szalai, Krisztina; Weichselbaumer, Michael; O’Hehir, Robyn E; Jensen‐Jarolim, Erika

doi:10.1111/cea.12031

Cited by 32 publications

(40 citation statements)

References 43 publications

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“…These observations that point towards the importance of conformational as opposed to linear epitopes are in line with recent observations that conformational epitopes rather than linear epitopes are critical for binding of IgE and for activation of IgE-sensitized basophils and/ or mast cells [48, 51, 52]. As reported by Albrecht and colleagues [48], peptides of Ara h 2 were unable to block cross-linking of IgE and cell activation by Ara h 2.…”

Section: Discussionsupporting

confidence: 86%

Epitope analysis of Ara h 2 and Ara h 6: characteristic patterns of IgE‐binding fingerprints among individuals with similar clinical histories

Otsu

Guo

Dreskin

2015

Clin Experimental Allergy

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Summary Background Ara h 2 and Ara h 6 are moderately homologous and highly potent peanut allergens. Objective To identify IgE-binding linear epitopes of Ara h 6, compare them to those of Ara h 2, and to stratify binding based on clinical histories. Methods Thirty highly peanut-allergic subjects were stratified by clinical history. Sera were diluted to contain the same amount of anti-peanut IgE. IgE binding to overlapping 20-mer peptides of Ara h 2 and Ara h 6 was assessed using microarrays. Results Each subject had a unique IgE-binding fingerprint to peptides; these data were coalesced into epitope binding. IgE from subjects with a history of more severe reactions (n = 19) had a smaller frequency of binding events (BEs) for both Ara h 2 (52 BEs of 152 (19×8epitopes) possible BEs and Ara h 6 (13 BEs of 133 (19×7 epitopes) possible BEs) compared to IgE from those with milder histories (n = 11) (Ara h 2: 47 BEs of 88 (11×8 epitopes) possible BEs, P < 0.01; Ara h 6: 25 BEs of 77 (11×7 epitopes) possible BEs, P < 0.001). Using an unsupervised hierarchal cluster analysis, subjects with similar histories tended to cluster. We have tentatively identified a high-risk pattern of binding to peptides of Ara h 2 and Ara h 6, predominantly in subjects with a history of more severe reactions (OR = 12.6; 95% CI: 2.0–79.5; P < 0.01). Conclusions and Clinical Relevance IgE from patients with more severe clinical histories recognize fewer linear epitopes of Ara h 2 and Ara h 6 than do subjects with milder reactions and bind these epitopes in characteristic patterns. Close examination of IgE binding to epitopes of Ara h 2 and Ara h 6 may have prognostic value.

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Section: Discussionsupporting

confidence: 86%

Epitope analysis of Ara h 2 and Ara h 6: characteristic patterns of IgE‐binding fingerprints among individuals with similar clinical histories

Otsu

Guo

Dreskin

2015

Clin Experimental Allergy

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“…This suggests that both types of modification are able to strongly reduce allergenicity. A recent study, using RBL cells, showed a reduction of 10–25% in RBL degranulation upon RA modification of Ara h 2 . In our study, with both Ara h 2 and Ara h 6, we showed a median reduction of more than 90%.…”

Section: Discussionsupporting

confidence: 66%

Chemical modification of peanut conglutin reduces IgE reactivity but not T cell reactivity in peanut‐allergic patients

Hoffen

Kleij

Jäger

et al. 2014

Clin Experimental Allergy

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“…(15) The 3-dimensional folds determine the IgE epitopes which are lost upon unfolding. (18) More recently, the structure of Ara h 2 was determined by X-ray crystallography and molecular modeling studies predict that half of the residues on the surfaces of both proteins are conserved. (19) These factors contribute to the difficulty in obtaining purified natural Ara h 6 (nAra h 6) that is free of Ara h 2.…”

Section: Introductionmentioning

confidence: 99%

Ara h 6 Complements Ara h 2 as an Important Marker for IgE Reactivity to Peanut

Koid

Chapman

Hamilton

et al. 2013

J. Agric. Food Chem.

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The similarities of two major peanut allergens, Ara h 2 and Ara h 6, in molecular size, amino acid sequence, and structure have made it difficult to obtain natural Ara h 6 free of Ara h 2. The objectives of this study were to purify natural Ara h 6 that is essentially free of Ara h 2 and to compare its IgE reactivity and potency in histamine release assays to Ara h 2. SDS-PAGE of the highly purified allergen (<0.01% Ara h 2) revealed a single 14.5kD band and the identity of Ara h 6 was confirmed by LC-MS/MS. Ara h 6 showed a higher seroprevalence in chimeric-IgE ELISA (n=54), but a weaker biological activity in basophil histamine release assays than Ara h 2. Purified Ara h 6 will be useful for diagnostic IgE antibody assays, as well as molecular and cellular studies to investigate the immunological mechanisms of peanut allergy.

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An unfolded variant of the major peanut allergen Ara h 2 with decreased anaphylactic potential

Abstract: Reduced/alkylated Ara h 2 might be a safer alternative than native Ara h 2 for immunotherapeutic treatment of peanut allergic patients.

Cited by 32 publications

References 43 publications

Epitope analysis of Ara h 2 and Ara h 6: characteristic patterns of IgE‐binding fingerprints among individuals with similar clinical histories

Epitope analysis of Ara h 2 and Ara h 6: characteristic patterns of IgE‐binding fingerprints among individuals with similar clinical histories

Chemical modification of peanut conglutin reduces IgE reactivity but not T cell reactivity in peanut‐allergic patients

Ara h 6 Complements Ara h 2 as an Important Marker for IgE Reactivity to Peanut

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