IgE cross-reactivity between the major peanut allergen Ara h 2 and the non-homologous allergens Ara h 1 and Ara h 3

Authors: BUBLIN, MERIMA - University Of Vienna; KOSTADINOVA, MARIA - University Of Vienna; RADAUER, CHRISTIAN - University Of Vienna; HAFNER, CHRISTINE - Karl Landsteiner Institute Of Dermatological Research; SZEPFALUS, ZSOLT - University Of Vienna; VARGA, EVA MARIA - Medical University Of Graz; Maleki, Soheila; VOGEL, LOTHAR - Paul-Ehrlich Institute; VIETHS, STEFAN - Paul-Ehrlich Institute; HOFFMAN-SOMMERGRUBER, KARIN - University Of Vienna

Submitted to: Journal of Allergy Clinical Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2013
Publication Date: 7/5/2013
Citation: Bublin, M., Kostadinova, M., Radauer, C., Hafner, C., Szepfalus, Z., Varga, E., Maleki, S.J., Vogel, L., Vieths, S., Hoffman-Sommergruber, K. 2013. IgE cross-reactivity between the major peanut allergen Ara h 2 and the non-homologous allergens Ara h 1 and Ara h 3. Journal of Allergy Clinical Immunology. 132(1):118-124.

Interpretive Summary: Ara h 1, Ara h 2, and Ara h 3, are major peanut allergens. Ara h 2 is an important predictor of clinical reactivity to peanut, but co-sensitization to all three allergens is correlated with the severity of patients’ symptoms. We investigated whether co-sensitization to these three allergens is caused by immunoglobulin E (IgE) cross-reactivity, despite the fact that they do not display obvious structural or amino acid sequence similarities. Multiple cellular and molecular immunological experiments were performed with purified Ara h 1, Ara h 2, and Ara h 3, and serum IgE from 10 peanut-allergic subjects. Ara h 1 completely inhibited IgE binding to Ara h 2 (median 96%) and Ara h 3(median 100%), whereas, IgE binding to Ara h 1 and Ara h 3, was partially inhibited by Ara h2 (medians 81% and 73%). IgE binding affinity for Ara h 2 was greater than for Ara h 1 and Ara h 3. A comparison of sequences showed that these non-homologous peanut allergens contain several similar surface exposed peptides. IgE binding to Ara h 2-derived peptides was completely inhibited by Ara h 1 and Ara h 3. A mixture of these peptides reduced the capacity of the three allergens to induce histamine release (12-49%). Occurrence of similar amino acid sequences in the three major peanut allergens account for the high extent of cross-reactivity among them.

Technical Abstract: Ara h 1, a vicilin, Ara h 2, a 2S albumin, and Ara h 3, a legumin, are major33 peanut allergens. Ara h 2 is an important predictor of clinical reactivity to peanut, but co-sensitization to all three allergens is correlated with the severity of patients’ symptoms. We investigated whether co-sensitization to these three allergens is caused by IgE cross-reactivity, despite the fact that they do not display obvious structural or sequence similarities. IgE cross-inhibitions were performed using purified Ara h 1, Ara h 2, and Ara h 3, and sera from 10 peanut-allergic subjects. Following an in silico search for similar peptides, IgE binding inhibition and basophil activation assays, using synthetic peptides were performed. Ara h 1 completely inhibited IgE binding to Ara h 2 (median 96%) and Ara h 3 (median 100%), whereas, IgE binding to Ara h 1 and Ara h 3, was partially inhibited by Ara h 2 (medians 81% and 73%). IgE binding affinity for Ara h 2 was greater than for Ara h 1 and Ara h 3. A comparison of sequences showed that these non-homologous peanut allergens contain several similar surface exposed peptides. IgE binding to Ara h 2-derived peptides was completely inhibited by Ara h 1 and Ara h 3. A mixture of these peptides reduced the capacity of the three allergens to induce mediator release (12-49%). Occurrence of similar sequences in the three major peanut allergens account for the high extent of cross-reactivity among them.