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. Peanut allergy usually begins in childhood and persists throughout the affected individual’s lifetime however, approximately 20% of young children develop tolerance.
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%. The prevalence of Ara h 1 sensitization was estimated to be 43% from a larger study using 12,155 serum samples in the USA. Ara h 1 is considered to be one of the major peanut allergens.
It is estimated that 97% of peanut allergy patients are sensitized to at least one of the allergens Ara h 1, 2 and 3. 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%). Similarly, in another study involving 30 peanut-allergic individuals, 16 patients (53%) were sensitized to Ara h 1.
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 1 is a storage protein, individuals who are sensitized to this component are at an increased risk for more severe symptoms and anaphylactic reactions. 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. 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.
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. 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. 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.
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. The peanut-related symptoms included oral symptoms, urticaria and angioedema.
Cosensitization to Ara h 1, 2 and 3 is caused by the IgE cross-reactivity between them.
Diagnostics
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. 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%. 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. 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.
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.
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. The high extent of cross-reactivity between Ara h 1, 2 and 3 is due to these components having similar sequences.
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. 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. 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%.
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. In addition, an IgE-binding cross-reactivity was discovered with the lentil and pea vicilins, Len c 1 and Pis s 1, respectively. 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.
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.
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