f422 Ara h 1

Summary

Ara h 1 is a vicilin seed storage protein and a member of the 7S globulin family capable of withstanding the harsh conditions of the gastrointestinal tract. Ara h 1 is a highly abundant seed storage protein and accounts for approximately 20% of the total protein content of peanut. 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 1 are at an increased risk for more severe symptoms and anaphylactic reactions. Roasting peanuts at high temperatures can increase the allergenicity of Ara h 1. Polysensitization to Ara 1, 2 and 3 can help to predict the severity of reaction at challenge. The use of specific IgE to Ara h 1 in combination with Ara h 2 and 3 could be helpful to diagnose individuals with peanut allergy. Cross-reactivity with other legume and tree nuts, and the seed storage proteins Ara h 2 and 3, have been reported with Ara h 1.

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 (1). Peanut allergy usually begins in childhood and persists throughout the affected individual’s lifetime however, approximately 20% of young children develop tolerance (2).

Ara h 1 had the second highest frequency of specific IgE binding (65%) in 40 peanut-allergic patients compared to the other peanut allergen components Ara h 2, 3, 5, 6 and 7, with Ara h 2 being the highest at 85% (3). The prevalence of Ara h 1 sensitization was estimated to be 43% from a larger study using 12,155 serum samples in the USA (4). Ara h 1 is considered to be one of the major peanut allergens (5, 6).

It is estimated that 97% of peanut allergy patients are sensitized to at least one of the allergens Ara h 1, 2 and 3 (6). A study by Flinterman et al. (2007) examining the IgE reactivity to major peanut allergens in 20 peanut-allergic children found that all of them showed IgE reactivity to Ara h 2. Ara h 6 was recognized by 16 children, and Ara h 1 and 3 by 10 children (50%) (7). Similarly, in another study involving 30 peanut-allergic individuals, 16 patients (53%) were sensitized to Ara h 1 (8).

Environmental Characteristics

Source and tissue

Ara h 1 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 with Ara h 1 accounting for an estimated 20% (9). Ara h 1 belongs to the vicilin protein family, also known as 7S globulin which is within the cupin protein superfamily (10). 

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 (11). Since Ara h 1 is a storage protein, individuals who are sensitized to this component are at an increased risk for more severe symptoms and anaphylactic reactions (12). 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 (13). 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 (13).

A study found specific IgE was positively correlated with clinical severity and Ara h 1 in adult patients (r = 0.74, P < 0.001) but this trend was not observed in children (14). In addition, another study found that sensitization to Ara h 2 and Ara h 1 and/or Ara h 3 appeared to be predictive of more severe reactions (15). 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 (16).

Cross-reactive Molecules

A study involving three patients with a history of anaphylaxis to peas also demonstrated peanut-related symptoms, highlighting that clinically relevant cross-reactivity between pea and peanut does occur and is due to the vicilin homologues, Pis s 1 and Ara h 1 (17). The peanut-related symptoms included oral symptoms, urticaria and angioedema (17).

Cosensitization to Ara h 1, 2 and 3 is caused by the IgE cross-reactivity between them (18).

Molecular Aspects

Biochemistry

Ara h 1 is a 64 kDa vicilin (7S globulin) protein belonging to the cupin superfamily which provides nourishment for seedling growth (10, 19). With trypsin inhibitory activity, it has been suggested that Ara h 1 may have a role in plant defense against insects (20). The vicilins are usually disc-shaped trimeric proteins, however, the subunits vary depending on the extent of posttranslational proteolytic processing and glycosylation (10). Ara h 1 contains a glycosylation motif in the C-terminal region on which a heterogeneous assortment of N-glycans with the structure, Man5–6Glc NAc2 or Man3–4XylGlcNAc2 is conjugated through asparagine (21). Ara h 1 is the only peanut allergen with a xylosylated N-Glycan (21)

Roasting peanuts at high temperatures allows for the formation of globular protein aggregates which are able to increase the allergenicity of Ara h 1 (12) however, boiling peanuts decreases the IgE binding capacity of the allergen component (20). Ara h 1 bound increased levels of IgE and was more resistant to heat and gastrointestinal digestive enzymes after undergoing the Maillard reaction (22). The Maillard reaction occurs during the processing or browning of food and is important for developing the flavor and color of peanuts (22). It has been proposed that the six cysteine residues could help Ara h 1 withstand digestive denaturation (20).

Isoforms, epitopes, antibodies

There is one isoform of Ara h 1, Ara h 1.0101 (19). 

Cross-reactivity

Cross-reactivity with other legume and tree nuts, and the seed storage proteins Ara h 2 and 3, has been reported with Ara h 1 (10). The high extent of cross-reactivity between Ara h 1, 2 and 3 is due to these components having similar sequences (18).

Although Ara h 1 and the cashew vicilin, Ana o 1 share 27% identity and 45% similarity in amino acid sequence, there is a lack of sequence conservation with respect to their linear epitopes (23). However, sera from peanut-allergic patients that react with Ara h 1 often also react with the vicilins from walnut, hazelnut and cashew nut known as Jug r 2, Cor a 11 and Ana o 1, respectively (24). In addition, the walnut vicilin, Jug r 2 has IgE-binding epitopes which are structurally similar to Ara h 1 and they share a sequence identity of 54% (25).

7S globulins are found in other legumes. For example, soybean beta-conglycinin, Gly m 5, is the closest known homolog of Ara h 1, demonstrating a similar 3D structure and 51% amino acid sequence identity (26). In addition, an IgE-binding cross-reactivity was discovered with the lentil and pea vicilins, Len c 1 and Pis s 1, respectively (27). Also, the β-conglutin precursor of lupine has been found to be significantly homologous to Ara h 1, with an identity ranging from 50 to 76%, and a homology between 63 and 93% but this is not of clinical significance (28, 29).

Ses i 3, the 7S vicilin-type globulin found in sesame seeds has 36% homology to Ara h 1 however, one of the IgE-binding epitopes has 80% homology with the equivalent region of the sesame seed vicilin (30). 

Diagnostic Relevance

Disease Severity

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 (16). 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% (31). 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 (15). The results of a recent meta-analysis identified that specific IgE to Ara h 1, 2 and 3 are highly specific for peanut allergy in children (32). 

Cross-Reactivity

Often, specific IgE measurements for Ara h 1 and Ara h 3 are not necessarily due to the high level of cross-reactivity between them and monosensitization to these seed storage allergen components is uncommon (12).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Magnus Borres

Last reviewed: December 2020