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Whole Allergen

f256 Walnut

f256 Walnut Scientific Information

Type:

Whole Allergen

Display Name:

Walnut

Route of Exposure:

Ingestion

Family:

Juglandaceae

Latin Name:

Juglans spp.

Summary

Walnut is monoecious, drought-tolerant, big tree plant, abundantly found in California. This tree is well established in the southern California coast range, transverse ranges, peninsular ranges, and the central valley. It is possible to become allergic to both the pollen and the fruit of this tree. Walnut food allergy has been reported in the countries of Northern America, Europe, Asia, etc. Walnuts can cause sensitization through ingestion as well as through inhalation of pollens or dust particles in processing industries. Major of walnut food allergens are from the 2S albumin and profilin family, which are named Jug r 1 to Jug r 7 sequentially. In IgE-mediated allergy to walnut common symptoms observed are nausea, vomiting, pruritus, abdominal pain urticaria, angioedema, diarrhea, asthma and anaphylaxis. Black walnut tree syrup is not allergenic to individuals with a walnut allergy. Walnut and pecan are species from the same family Juglandaceae. Due to cross-reactive allergens from walnut and pecan, many physicians advise restricting both nuts from the diet.

Allergen

Nature

Walnut tree (Juglans. spp) is known as a California big tree that grows in moist to dry soil (1). Harvesting of Walnut starts in late August and further process of green hulls drying and then splitting continues till late November (2). It can grow erect and spread widely. Thus it requires ample growing space. It measures 15-30 feet high and 15-30 feet in width. It can live between 50 to 150 years. The color of the leaves can be green, golden, yellow, or orange. It has a monoecious type of reproductive system (female and male reproductive parts on the same tree). Fruits are edible with a size of 1.50 to 3.00 inches (1).  The amount of walnut produced by California for 2019 was 630,000 tons, (3). The nature of the fruit is a hard, fibrous outer layer and soft fleshy inner part. Walnut’s shell has three parts, a sclereid layer, a sclerenchyma layer and a shrunken cell layer. These layers are linked in this sequence from the outer layer to the inner layer (4). The Walnut itself is enclosed in a thin edible skin known as pellicle (5).

Habitat

Walnut is generally found in the coast range, transverse ranges, peninsular ranges, and the central valley like in Southern California (6). It grows in the drought-tolerant area, loam, or arenaceous soil and can grow under highly acidic to alkaline soil pH (1). Walnut prefers to grow in singular stands instead of co-existing with other similar tree species. Optimal condition to growth includes a warm environment with a sheltered site. It requires ambient light to grow and is sensitive to winter and late spring frosts. Adult trees can withstand a hard time in winter at -30º C (7). 

Taxonomy

Walnut belongs to the botanical family of Juglandaceae with 24 different species. (8). The taxonomical hierarchy can be presented as (Figure 1A & 1B)

Epidemiology

Worldwide distribution

Tree nut allergy affecting roughly 0.5 to 1% of the US population. Among all nut allergens, the prevalence of walnut allergy was 37%-48% in the US, 34% in Turkey, 32% in France, 24% in the UK, and 5% in Denmark. (13). In a European food allergy study, the highest prevalence of walnut allergy is found in France (3.7%), while the prevalence for Italy, Spain and Germany was 3.1%, 3.1% and 3.3% respectively. (8). Walnuts and food products made from walnut are widely used in Japan and can induce anaphylaxis. In a study by Santo, Yamamoto 2017, 39% of children were reported to have a history of walnut allergy. Among these, the most prevalent cases were reported for atopic dermatitis (59%) and asthma (33%) (14). A study was conducted in Japan with 1383 patients. The survey questionnaire was designed for allergic symptoms for food allergies. Out of  319 cases reporting food allergic reactions, 9 (2.8%) cases reported walnut as the offending allergen  (15).

Risk factors

In the US, the estimated prevalence of childhood food allergy was 7.6 % in 2018, out of which walnut allergy was 0.6%. Among children with food allergies, the prevalence of walnut allergen was 8.3%. (16). Around 2-4% of children in developed countries are affected by food allergies and strongly impacts their quality of life. In Chile, a study indicated that allergy to walnut allergy was observed around 1.3% in school aged children (n=455). In the same study, 13% (n=63) of children were having recurrent reactions due to food allergies, out of which 10% were reported to suffer from walnut allergy recurrence (17). 

Environmental Characteristics

Worldwide distribution

Walnut trees grow in South Europe, Central Asia and Western Asia, especially from the Mediterranean. From India and other parts of Asia, its occurrence is majorly found in the west part of Himalaya mountain chains from Kashmir to Kyrgyzstan and Tajikistan. It is widely cultivated across the northern hemisphere, and in most of Europe apart from northern regions, Turkey ranked at third position after China and the US in the production of walnut. It is also introduced in America, Africa, Australia and New Zealand, (7).

Route of Exposure

Main

Walnut's food allergy is caused by its nut ingestion (18).

Secondary

Skin sensitization through food is also associated with severe reactions (19).

Detection

Environmental source

Powdered walnut shells are used for many commercial, industrial purposes. It is used for metal polishing in the aeronautical industry and as a cleaning agent for automobile and jet engines, electronic circuit boards, and paint graffiti  (20). Walnut oil can be one of the ingredients for making paint, due to its properties of the effective binding medium and adsorptive property towards thallium or other metal ions. Biochemicals and dyes from walnut are non-toxic and have clear and glossy consistency. Walnut husk is used in the production of experimental dye like methylene blue which can be used for dyeing fabrics and other purposes (21). All these factors or formulations of walnut can trigger an allergic reaction through the environmental source. 

Main methods

Various kinds of detection methods based on proteins or DNA are available to analyze concealed walnut components in food products prepared with or near walnuts (8).

Clinical Relevance

Food allergen and anaphylaxis

Common symptoms found in walnut allergy are nausea, vomiting, pruritus, abdominal pain urticaria, angioedema, diarrhea, asthma and anaphylaxis. In adults, oral allergy syndrome (pollen-associated food allergy) is the most usual clinical manifestation concern. Anaphylaxis and potentially fatal allergic reactions are the most severe systemic observation under IgE-mediated responses to walnut. An anaphylactic reaction can be observed immediately after ingestion of the offending food and can lead to life-threatening condition (8).

Asthma

Sato, Yamamoto et al conducted a study in which 33% out of 60 allergenic cases were diagnosed with asthma with 39 % of 108 patients reported allergy history towards walnut. IgE level for Jug r 1 was higher in children with anaphylactic shock or lower respiratory symptoms than children with moderate allergy. Moderate allergy symptoms found were skin, digestive, and upper respiratory dysfunction (14).

Diagnostics Sensitization

Challenge test

A study by Andorf and Borres evaluated 60 multifood allergic cases by evaluating IgE levels in serum for allergen components. On the basis of the correlation of sIgE and SPT values, it is reported that all cases were significantly allergenic towards both walnut and pecan. This concludes that walnut allergic patients are mostly allergic to pecan (22).

Prevention and Therapy

Allergen immunotherapy

In a prospective cohort study by Elizur et al 2018, oral walnut immunotherapy is able to establish desensitization to walnut and cross desensitization to pecan and hazelnut with an effective safety profile. A small amount of allergenic dose every day for the period of the treatment may be able to induce desensitization. The treatment enrolled 73 patients out of which 55 underwent oral immunotherapy (OIT) and 18 were the control group under dietary restrictions. Among the patients undergoing OIT, 49 were completely desensitized while 3 had partial desensitization towards walnut and the remaining 3 were not able to complete the treatment course. The 18 cases from the control group were still walnut allergic, out of these 9 underwent OIT with 7 of them achieving complete desensitization to walnut. At 6 month follow-up, 56 patients desensitized to walnut and some of them showed co-desensitization to pecan and hazelnut (23). 

Prevention strategies

The tree syrup from black walnut is promoted due to the prevalent distribution of this tree throughout the Midwest and the South American States. The study by Lierl, Assa'ad et al, concluded that black walnut tree syrup is not allergenic even in patients with walnut sensitivity (24).

Walnut or any tree nut allergy is difficult to cure, but preventive measures can be taken care of in allergenic food. Strict avoidance of allergenic nuts and products that might contain nuts can protect against allergic reactions. The guidelines proposed by the British Society for Allergy and Clinical Immunology (BSACI) stated that the restriction of all nuts is difficult to achieve and can result in a severely restricted diet. They advised continuing with eating nuts that can be tolerated and to avoid all nut exposure when eating out of home because of the risk of cross-contamination and misconception. Food allergy increases stress and anxiety in children which leads to a detrimental impact on the quality of life. Children may constantly live in fear of severe allergenicity and fatal reactions and hence require to maintain constant vigilance when making food choices (25).

Other topics

After ensuring a strict avoidance diet, individuals with nut allergies can still be at risk of suffering allergic symptoms because of unknown exposure to the hidden allergen. During food processing, incorrect labeling or cross-contamination can lead to these causes. Thus, labeling compliances, industrial food allergenic management, customer safety standards,  precise and sensitive analytical practices need to be implemented (8).

Molecular Aspects

Allergenic molecules

Prolamin and Cupin are two superfamilies for walnut allergens. prolamin proteins include Jug r 1, Jug n 1 and Jug r 3 while the Cupin family hasJug r 2, Jug n 2 and Jug r 4 proteins. Recently, another allergen (Jug r 5) was identified from profilins family (8).

Allergen

Biochemical name

Molecular Weight (kDa)

Allergenicity/ clinical relevance

Jug r 1

2S albumin seed storage protein

15-16

In a study observed among patients with systemic allergic reactions to walnuts (n=16), 75% showed IgE binding to Jug r 1 (26)

Jug r 2

Vicilin seed storage protein

44

In a study,9 out of 15 patients with walnut allergy showed Jug r 2 binding with patient’s serum IgE (27)

Jug r 3

Non-specific lipid transfer protein type 1 (nsLTP1)

9

91.3% of patients were found with allergenicity towards walnut and showed IgE binding to LTP from walnut extract. (28)

Jug r 4

11S globulin seed storage protein

58.1

Among walnut allergic patients, 57% were observed to bound to Jug r 4 (29).

Jug r 5

PR-10

20

In two food challenges using walnut observed 9 and 5 positives were also birch sensitized. The study evidenced that the PR-10 expressed by the nut inhibited the 20 kDa IgE band in walnut extract (26).

Jug r 6

Vicilin-like cupin

47

19 from 76 walnut allergic patients sera showed IgE binding to 47 kDa, vicilin-like protein (26).

Jug r 7

Profilin

13

A EuroPreval study observed 47 out of 217 walnut sensitized subjects showed IgE binding (26).

Jug r 8

ns-LTP-2

9

Among 10 walnut allergic subjects, four were positive in IgE binding to the protein, expressed in Pichia (26).

Allergen

Biochemical name

Molecular Weight (kDa)

Allergenicity/ clinical relevance

(8,26)

Biomarkers of severity

Walnut has a group of allergenic proteins that are heat and digestion stable and therefore connected with a high risk of eliciting systemic reactions. Jug r 3 is known as a non-specific lipid transfer (LTP) stable protein and is resistant to denaturation and proteolytic reaction. Evidence of serum IgE for  Jug r 3 indicates local symptoms and systemic reaction. Specific IgE to Jug r 1 and Jug r 2 are associated with risk for systemic reactions (8).

Cross-reactivity

Cross-reactivity between walnut allergens and birch allergens may occur because of similarity markers like Bet v 2 (profilin) and Bet v 1 (PR-10) (30). In a study by Wangorsch, Jamin et al IgE cross-reactivity of Jug r 5 and Bet v 1 was reported (30).

Recurrent cross-reactivity was found with pistachio, hazelnut, Brazil nut, chestnut, pine nut and other plant species like quinoa, sesame, buckwheat, and soybean. (8). Cross-reactivity of walnut and mustard, hazelnut and Brazil nut has been reported in serum IgE level. 

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Magnus Borres

 

Last reviewed: November 2020

References
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