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|Biological Function||2S albumin trypsin inhibitor|
|Route of Exposure||Ingestion|
|Source Material||Peanut extract|
|Latin Name||Arachis hypogaea|
|Categories||Food Of Plant Origin, Legumes|
|Molecular Weight||17 kDa|
Ara h 2 is considered to be one of the major peanut allergens. Ara h 2 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. It is estimated that 97% of peanut allergy patients are sensitized to at least one of the allergens Ara h 1, 2 and 3. Individuals who are sensitized to Ara h 2 are at an increased risk for more severe symptoms and anaphylactic reactions, with Ara h 2 being one of most potent, and frequently recognized peanut allergens. Polysensitization to Ara 1, 2 and 3 can help to predict the severity of reaction at challenge. Roasting peanuts at high temperatures increases the allergenicity of Ara h 2. Studies have reported that specific IgE to Ara h 2 can be important in diagnosing peanut allergy in combination with Ara h 1 and 3, or with Ara h 6. Specific IgE to Ara h 2 has been a proposed biomarker to help predict the severity of peanut allergic reactions, although studies have demonstrated conflicting results. However, the authors of a recent meta-analysis suggested that specific IgE to Ara h 2 can reduce the number of oral food challenges in unclear cases and has high diagnostic accuracy for peanut allergy in children across geographic locations. Peanut and tree nuts show cross reactivity in peanut-allergic patients because Ara h 2 shares IgE-binding epitopes with almond and Brazil nut allergens.
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 (1). Peanut allergy usually begins in childhood and persists throughout the affected individual’s lifetime however, approximately 20% of young children develop tolerance (2).
Typically, the frequency of Ara h 2 sensitization is higher compared to other peanut allergen components. For example, Ara h 2 had the highest frequency of specific IgE binding (85%) in 40 peanut-allergic patients compared to the other peanut allergen components Ara h 1, 3, 5, 6 and 7 (3). The prevalence of Ara h 2 sensitization from a larger study using 12,155 serum samples in the USA was estimated to be 62%, similarly this was higher than the other allergen components (4). In contrast, a study involving 30 peanut-allergic individuals found that 83% (25/30) of patients with a positive skin prick test (SPT) were sensitized to Ara h 2, with the prevalence of Ara h 6 sensitization being slightly higher at 87% (26/30) (5).
Ara h 2 is considered to be one of the major peanut allergens (6, 7). It is estimated that 97% of peanut allergy patients are sensitized to at least one of the allergens Ara h 1, 2 and 3. In addition, a UK study found that 84% (42/50) were sensitized to Ara h 2 and 6, with 74% (31/42) having higher levels of Ara h 2-specific IgE than Ara h 6-specific IgE (7). 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 (8). A review by van der Valk et al. (2016) summarized studies assessing the prevalence of cosensitization with Ara h 2 and 6 which ranged from 0 to 90% (e.g. 0, 45, 59, 71, 73, 74, 80, 90%) (9).
Ara h 2 is a highly abundant seed storage protein and is structurally stable (4). The allergens Ara h 1, 2 and 3 provide >30% of the total protein content of peanuts (10). Ara h 2 is a member of the 2S albumin family and therefore belongs to the prolamine protein superfamily (11). 2S albumins are found in the seeds of many mono- and dicotyledon plants where they provide amino acids for growing seedlings and have a role in pathogen defense (12, 13).
Typical clinical symptoms of peanut allergy range from angioedema, urticaria, nausea, abdominal pain, vomiting, wheezing, and breathlessness which usually occur soon after peanut ingestion (14). Since Ara h 2 is a storage protein, individuals who are sensitized to this component are at an increased risk for more severe symptoms and anaphylactic reactions (15). Ara h 2 and Ara h 6 are considered to be the most potent peanut allergens (16). Sensitization to peanut storage proteins, Ara h 1, 2 and 3 was associated with increased quantities of airway and systemic inflammation markers compared to patients who were not sensitized to these peanut allergen components in a population of asthma sufferers (17). Food hypersensitivity symptoms were also more regularly reported by those sensitized to Ara h 1, 2 and 3 than by any other participants in the study (17).
In 2010, a study reported that Ara h 2 could be a useful tool to help predict peanut allergy (18). Another study found specific IgE was positively correlated with clinical severity and Ara h 2 in adult patients (r = 0.63, P = 0.002) but this trend was not observed in children (19). Kukkonen et al. (2015) found that all of the severely allergic patients were sensitized to Ara h 2 or 6 and this was not associated with age (participant age ranged from 6 to 18 years old) (20). In addition, a study found that sensitization to rAra h 2 and rAra h 1 and/or rAra h 3 appeared to be predictive of more severe reactions (21). Similarly, the results of a recent study in Australia found that polysensitization to Ara 1, 2 and 3 can help to predict the severity of reaction at challenge (22).
Similarities in physicochemical properties to known IgE epitopes of 2S albumins could account for clinically observed cross-sensitivity between peanuts and tree nuts (23).
Ara h 2 is a 17 kDa conglutin seed storage protein (24, 25). Ara h 2 is a member of the 2S albumin family and therefore belongs to the prolamine protein superfamily (11). Ara h 2 shares amino acid sequence identity with other 2S albumin peanut allergens, Ara h 6 and Ara h 7 (59% and 42%, respectively) (13). 2S albumins are thought to sensitize directly in the gastrointestinal tract, which is possible despite the harsh conditions due to the high stability of their intrinsic protein structure, consisting of a well-conserved skeleton of cysteine residues (26).
The structure of Ara h 2 is critical in terms of its allergenic potential because disruption of the disulfide bonds alters the IgE binding capacity (13). Roasting peanuts at high temperatures allows for the formation of globular protein aggregates which increase the allergenicity of Ara h 2 (15) however, boiling peanuts decreases the IgE binding capacity of the allergen component (27). Ara h 2 bound increased levels of IgE and was more resistant to heat and gastrointestinal digestive enzymes after undergoing the Maillard reaction (28). The Maillard reaction occurs during the processing or browning of food and is important for developing the flavor and color of peanuts (28).
There are two isoforms of Ara h 2, Ara h 2.0101 and Ara h 2.0201 (24). Research directed at defining the epitopes of Ara h 2 that are bound by IgE from peanut-allergic patients has shown that most IgE binds to conformational epitopes rather than by linear epitopes. Conformational epitopes are those generated by the native folding of the Ara h 2 polypeptide whereas linear epitopes are consecutive amino acids that do not depend on polypeptide folding (25). Five of seven IgE-binding linear epitopes of Ara h 2 share 70-93% homology to similar regions of Ara h 6 (29). Otsu et al. (2014) hypothesized that Ara h 6 is more tightly folded compared to Ara h 2 making conformational IgE-binding epitopes less cross-reactive than the highly homologous linear epitopes (29, 30).
Peanut and tree nuts show cross-reactivity in 25 to 50% of peanut-allergic patients because Ara h 2 shares IgE-binding epitopes with almond and Brazil nut allergens (31). However, despite 2S seed albumin allergens sharing structural similarities, Ara h 2, showed no structural homology with the corresponding regions of Walnut Jug r 1, Pecan Car i 1 or Brazil nut Ber e 1 (32). Although there is a theory of cross-reactivity being dependent on allergens sharing a similar sequence and/or structure, there are experimental data highlighting a lack of relationship between the percentage of shared identity and the ability to bind IgE (23).
While specific IgE to Ara h 2 has been a proposed biomarker to help predict the severity of peanut allergic reactions, studies have demonstrated conflicting results (33). However, the authors of a recent meta-analysis publication suggested that specific IgE to Ara h 2 can reduce the number of oral food challenges in unclear cases and has high diagnostic accuracy for peanut allergy in children across geographic locations (34). Results from a cross-sectional study involving 222 Australian children reported that using a combination of Ara h 1, 2 and 3 for peanut component testing could be helpful to identify patients with peanut allergy (22). An earlier study found that using the combination of Ara h 1, 2, and 3 resulted in a higher specificity (94%) when diagnosing peanut allergy in Japanese children in comparison to using IgE to Ara h 2 alone resulting in a sensitivity and specificity of 88% and 84%, respectively. However, the sensitivity of using the combination of Ara h 1, 2, and 3 was 31% (35). A study found that cosensitization to rAra h 2 and rAra h 1 and/or rAra h 3 was predictive of more severe reactions in peanut allergy (21).
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 (7, 20). However, variation has been shown in the 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 (16).
Author: RubyDuke Communications
Reviewer: Dr. Magnus Borres
Last reviewed: December 2020