Redefining the major peanut allergens

Abstract

Food allergy has become a major public health concern in westernized countries, and allergic reactions to peanuts are particularly common and severe. Allergens are defined as antigens that elicit an IgE response, and most allergenic materials (e.g., pollens, danders, and foods) contain multiple allergenic proteins. This has led to the concept that there are “major” allergens and allergens of less importance. “Major allergens” have been defined as allergens that bind a large amount of IgE from the majority of patients and have biologic activity. However, the ability of an allergen to cross-link complexes of IgE and its high-affinity receptor FcεRI (IgE/FcεRI), which we have termed its allergic effector activity, does not correlate well with assays of IgE binding. To identify the proteins that are the most active allergens in peanuts, we and others have employed in vitro model assays of allergen-mediated cross-linking of IgE/FcεRI complexes and have demonstrated that the most potent allergens are not necessarily those that bind the most IgE. The importance of a specific allergen can be determined by measuring the allergic effector activity of that allergen following purification under non-denaturing conditions and by specifically removing the allergen from a complex allergenic extract either by chromatography or by specific immunodepletion. In our studies of peanut allergens, our laboratory has found that two related allergens, Ara h 2 and Ara h 6, together account for the majority of the effector activity in a crude peanut extract. Furthermore, murine studies demonstrated that Ara h 2 and Ara h 6 are not only the major elicitors of anaphylaxis in this system, but also can effectively desensitize peanut-allergic mice. As a result of these observations, we propose that the definition of a major allergen should be based on the potency of that allergen in assays of allergic effector activity and demonstration that removal of that allergen from an extract results in loss of potency. Using these criteria, Ara h 2 and Ara h 6 are the major peanut allergens.

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

“…This also explains the observation that the intensity of IgE binding to the peptides that contain the linear epitopes is also less for Ara h 6 than for Ara h 2. This is compatible with the observation that Ara h 6 has 5 disulphide bonds compared with 4 disulphide bonds for Ara h 2 and with our experience that proper folding of recombi-nant Ara h 6 is particularly important to preserve aller-genic activity [21]. …”

Allergenicity attributes of different peanut market types

“…No previously published data quantifying the Ara h 3 content of peanuts is available; however, the large quantity of Ara h 3 in peanut is nevertheless expected since the bands of Ara h 3 dominate the peanut protein profile as shown in this study (Figs. 1 and 2) and many other publications (Hefle et al, 1995;Koppelman et al, 2003;Fu and Maks, 2013;Zhuang and Dreskin, 2013). There are also no data on the amount of Ara h 6 in peanut.…”

Peanut allergens are rapidly transferred in human breast milk and can prevent sensitization in mice

“…In fact, these 2S albumins are the most seroprevalent in specific IgE immunoassays and the more potent ones in triggering effector cell activation in vitro and positive skin prick test in allergic patients (27,33,48,(49)(50)(51)(52)(53). Both Ara h 2 and Ara h 6 have been shown to be resistant to enzymatic digestion (54)(55)(56).…”