Ara h 8
Summary
Ara h 8 is a Bet v 1-homologous allergen and a member of the PR-10 protein group, and is typically associated with increased sensitization in areas with increased exposure to tree pollen. Ara h 8 is found in small quantities in peanuts and is unable to withstand digestive enzymes and pH conditions associated with the stomach. Bet v 1-related proteins like Ara h 8 generally cause mild symptoms, typically those associated with oral allergy syndrome, and there is evidence of individuals with monosensitization to Ara h 8 demonstrating tolerance to peanuts. Ara h 8 IgE is of limited diagnostic use in diagnosing a true peanut allergy, although it can be valuable when diagnosing peanut symptoms due to cross-reactions to birch pollen. Cross-reactivity has been shown with Bet v 1 (birch pollen) and its homologs Gly m 4 from soybean and Pru av 1 from Cherry, Fagales tree pollens and legumes of the Fabaceae family.
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.
A study in the USA reported regional IgE sensitization to Ara h 8 with people in the Northeastern states having a higher frequency. This was thought to be due to an increased exposure to tree pollen (e.g. birch) containing key allergens from the pathogenesis-related protein 10 (PR-10) family. These results are consistent with the results from a study conducted in Sweden and it has been reported that birch trees are responsible for a substantial divide between the North and the South in Europe with respect to cross-reactions to Ara h 8. However, an Australian study Kaur et al. discovered that the sensitization pattern for the small number of children sensitized to Ara h 8 in their study, did not correlate with the typical New South Wales grass pollen sensitization, and few children were highly sensitized to birch pollen by skin prick test. The authors of the USA study also found that sensitization to peanut storage proteins (Ara h 1, 2 and 3) was more common in children with suspected peanut allergy compared to adults, although the opposite was true for Ara h 8. The prevalence of Ara h 8 was 2.4%, 49.4% and 42.9% in children, adolescents and adults, respectively. Ara h 8 sensitization was detected in 21% of 192 peanut-allergic patients in the UK with a median age of five years. Another study reported a lower prevalence of IgE to Ara h 1, 3, and 8 (38–42% using the 0.35 kUA/l cut-off) compared to a high prevalence of IgE to Ara h 2 (88%) in Japanese peanut-allergic children. Lin et al. found that the percentage of Taiwanese preschool children who were IgE sensitized to Ara h 8 was the lowest at 13.8% compared to Ara h 1, 2, 3 and 9 (51.8%, 65.5%, 62.1%, and 24.1%, respectively).
Clinical Relevance
Owing to their heat lability, Bet v 1-related proteins like Ara h 8 generally cause mild symptoms, typically those associated with oral allergy syndrome.
A study in Sweden showed that monosensitization to Ara h 8 in 129 children (89.5%) was indicative of a tolerance to peanuts. However, three patients experienced systemic clinical signs at peanut challenge which raised the questions of whether these were rare cases and circumstances which triggered an allergic reaction or perhaps the patients were not truly monosensitized to Ara h 8. Similarly, Glaumann et al. (2015) concluded that children sensitized only to Ara h 8 and not to peanut storage proteins could be at risk for systemic allergic reactions when consuming larger quantities of peanuts, but may tolerate a small amount.
Cross-reactive Molecules
Cross-reactivities between Bet v 1, Ara h 8 and Gly m 4, the homolog from soybean, have been identified. Sensitization to Gly m 4 has been reported to cause systemic clinical signs in patients, in contrast to Ara h 8.
Diagnostics
Cross-reactivity
Due to the homology between Ara h 8 and the major birch pollen allergen, Bet v 1, cross-sensitization occurs which is also seen with other Fagales tree pollens. This could lead to patients who have an allergy to Fagales tree pollen being diagnosed with peanut allergy. The Ara h 8 specific IgE (sIgE) assay is unable to differentiate patients with peanut allergy and therefore should not be used in isolation. The authors suggested using Ara h 8 sIgE after a negative Ara h 2 sIgE result. More recently, the results of a meta-analysis study also found that Ara h 8 sIgE is of limited diagnostic use in diagnosing a true peanut allergy. IgE to Ara h 8 can be valuable to use when diagnosing peanut symptoms due to cross-reactions to birch pollen.
Cross-Reactivity
The Bet v 1 homologous peanut allergen Ara h 8, is thought to be involved in the cross-reactivity of peanut allergy patients. Twenty patients with peanut and birch pollen allergy, and a positive double-blind, placebo-controlled food challenge result to peanut, all experienced symptoms in the oral cavity, progressing to more severe symptoms in 40% of patients. Recombinant Ara h 8-specific IgE was demonstrated in 85% of patients, IgE binding to Ara h 8 was inhibited by Bet v 1 and rAra h 8 inhibited IgE binding to peanut in four of seven tested patient sera. The study concluded that peanut allergy might be mediated in a subgroup of the patients by cross-reactivity of Bet v 1 with the homologous peanut allergen Ara h 8. Similarly, examination of the sera of five patients in relation to four recombinant allergens led to the conclusion that IgE cross-reactivity existed between Bet v 1 (birch pollen) and its homologs Gly m 4 from soybean, Ara h 8, and Pru av 1 from Cherry, but variation in IgE specificity between patients was observed. In addition, Ara h 8 is involved in grass pollen-associated food allergy.
Lupins are an emerging cause of food allergy because of recent large-scale introduction as an additive to wheat flour or the use of lupin flour in processed foods and is frequently used in Europe and Australia. Lupins are legumes of the Fabaceae family with PR-10 white lupin sharing significant sequence homology and molecular similarity with the peanut allergen Ara h 8. Sanz et al. (2010) explained that in patients with clinical sensitization to a legume, particularly peanut, greater caution is required (depending on the population) with lupin cross-reactivity of approximately 5% in British and Norwegian populations, 17% to 68% for French and Belgian populations, and 32% for Danish populations.
References
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