Current and Emerging Immunotherapeutic Approaches to Treat and Prevent Peanut Allergy

Darren S Miller; Michael P Brown; Paul M Howley; John D Hayball


Expert Rev Vaccines. 2012;11(12):1471-1481. 

In This Article

Clinically Relevant Peanut Allergens

In general, food allergens are low molecular proteins or glycoproteins (less than 70 kD) that are soluble in aqueous solution and abundant in the food source. These molecules are generally resistant to proteases, heat and denaturants, thus preventing destruction during food preparation and digestion.[18,19] Eleven peanut allergens (Ara h 1-11) have been described in the literature, all of which have been sequenced and cloned.[20] These allergens have demonstrated either clinical reactivity in peanut allergic patients or are associated with reactivity to peanut allergy patient sera (Table 1). Ara h 1 was the first major peanut allergen identified,[21] and has an average molecular weight of 63.5 kD and an isoelectric point of 4.55. The gene for Ara h 1 has significant sequence homology with plant seed storage proteins of the vicilin family.[22] The second major peanut allergen characterized was Ara h 2,[23] which has a molecular weight of 17.5 kD, an isoelectric point of 5.2 and a 20% carbohydrate content. The sequence of the Ara h 2 gene revealed significant nucleotide homology with the conglutin seed storage protein family. Ara h 3, a member of the glycinin family of seed storage proteins, was the third allergen identified[24] and was found to bind to peanut-specific serum IgE in almost half of the peanut-allergic patient population.[25] Ara h 4 is highly homologous in amino acid sequence to Ara h 3 and has since been renamed Ara h 3.02.[201] Ara h 5 is a member of the profilin family.[26] Ara h 6 and h 7 are also members of the conglutin family,[26] and are thought to be various isoforms of Ara h 2. Ara h 6 has recently emerged as a major peanut allergen.[27] Ara h 8 is a major allergen in patients with both birch pollen and peanut allergy.[28] Ara h 9 is a newly discovered peanut allergen with clinical relevance for the Mediterranean allergic population.[29] Ara h 10 and Ara h 11 are also recently described isolates that have demonstrated some immunoreactivity against allergic patient sera and could potentially emerge as important peanut-associated allergens.

The three major allergenic proteins in peanuts, Ara h 1, Ara h 2 and Ara h 3, share common characteristics with many other allergenic food proteins: present in high concentrations, water soluble, and resistant to heat and digestion.[30] Although peanuts belong to the legume family, less than 15% of peanut-allergic patients react to proteins from other members of the legume family.[31] Interestingly though, tree nuts belong to a different botanical family, and yet 25–35% of patients who are allergic to peanuts also have allergic reactions to tree nuts.[10] The most common tree nuts that cause allergic reactions are Brazil nuts, almonds, hazelnuts, walnuts, almonds, pecans and cashew nuts.[14,32,33]