Ara h 6
Summary
Ara h 6 is a conglutin seed storage protein and member of the 2S albumin family which is capable of withstanding the harsh conditions of the gastrointestinal tract. Initially, Ara h 6 was not thought to be one of the major peanut allergens but now is considered to be one of the most potent. Individuals who are sensitized to Ara h 6 are at an increased risk for more severe symptoms and anaphylactic reactions. Peanut allergy patients who are sensitized to Ara h 6 are frequently also sensitized to Ara h 2 however, in rare cases, Ara h 6 sensitization without Ara h 2 sensitization may cause severe reactions to peanut. Using IgE specific to Ara h 2 and 6 can help to diagnose peanut allergy. Similarities in physicochemical properties to known IgE epitopes of 2S albumins could account for clinically observed cross-sensitivity between peanuts and tree nuts.
Epidemiology
Worldwide distribution
Studies have typically reported peanut allergy prevalence rates between 1–2% in Western nations. Peanut allergy appears to be less common in Asia and other global areas, although epidemiological studies in non-Western regions have been sparse. Peanut allergy usually begins in childhood and persists throughout the affected individual’s lifetime however, approximately 20% of young children develop tolerance.
In a study involving 30 peanut-allergic individuals, the majority of patients with a positive skin prick test (SPT) were sensitized to Ara h 2 (83%, n=25) and Ara h 6 (87%, n=26). A UK study found that 84% (42/50) were sensitized to Ara h 2 and 6. This is in agreement with an earlier study which concluded that Ara h 2 and 6 were the most frequently recognized major peanut allergens in children. A review by van der Valk et al. (2016) summarized the prevalence of cosensitization of Ara h 2 and 6 which ranged from 0 to 90% (e.g. 0, 45, 59, 71, 73, 74, 80, 90%) and monosensitization to Ara h 6 was uncommon.
Clinical Relevance
Typical clinical symptoms of peanut allergy range from angioedema, urticaria, nausea, abdominal pain, vomiting, wheezing, and breathlessness which usually occur soon after peanut ingestion. Since Ara h 6 is a storage protein, individuals who are sensitized to this component are at an increased risk for more severe symptoms and anaphylactic reactions. Ara h 2 and Ara h 6 are considered to be the most potent peanut allergens although compared to Ara h 1, 2 and 3, Ara h 6 was identified as a major peanut allergen more recently. Kukkonen et al. (2015) found that all of the severely peanut-allergic patients in their study were sensitized to Ara h 2 or 6.
In rare cases, Ara h 6 sensitization may occur without Ara h 2 and this could cause a severe reaction to peanut. A 15-year-old boy with a history of anaphylaxis was sensitized to Ara h 8 but not to Ara h 1, 2 or 3. During an open challenge to peanut, he experienced gastrointestinal and respiratory signs, and therefore treatment was provided. IgE blood testing revealed a doubling of IgE antibody concentration to peanut compared to a sample nine months earlier. With barely detectable levels of IgE antibody to Ara h 2 and 9, this prompted the analysis of Ara h 6 IgE sensitization and demonstrated a large sensitization despite a very modest level of IgE to Ara h 2.
Cross-reactive Molecules
Similarities in physicochemical properties to known IgE epitopes of 2S albumins could account for clinically observed cross-sensitivity between peanuts and tree nuts.
Diagnostics
Disease Severity
Hemmings et al. (2020) found that Ara h 2 and 6 specific IgE provided the greatest accuracy to diagnose peanut allergy which is in agreement with results from an earlier double-blind placebo-controlled study and an oral food challenge study in the Mediterranean region. However, variation has been shown in IgE cross-reactivity between Ara h 2 and 6 and therefore using a mixture of these two 2S albumins may improve diagnostic performance when trying to determine the severity of allergic symptoms. Although Ara h 6 monosensitization has been reported as uncommon, a study in Iceland demonstrated that two of six peanut-allergic patients who were Ara h 2 negative were monosensitized to Ara h 6.
References
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- Hemmings O, Du Toit G, Radulovic S, Lack G, Santos AF. Ara h 2 is the dominant peanut allergen despite similarities with Ara h 6. J Allergy Clin Immunol. 2020;146(3):621-30.e5.
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