Precautionary allergen labelling: perspectives from key stakeholder groups

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals. The lack of agreed reference doses has resulted in inconsistent application of PAL by the food industry and in levels of contamination that prompt withdrawal action by enforcement officers. So there is a poor relationship between the presence or absence of PAL and actual reaction risk. This has led to a loss of trust in PAL, reducing the ability of consumers with food allergies to make informed choices. The result has been reduced avoidance, reduced quality of life and increased risk‐taking by consumers who often ignore PAL. All contributing stakeholders agree that PAL must reflect actual risk. PAL should be transparent and consistent with rules underpinning decision‐making process being communicated clearly to all stakeholders. The use of PAL should indicate the possible, unintended presence of an allergen in a consumed portion of a food product at or above any proposed action level. This will require combined work by all stakeholders to ensure everyone understands the approach and its limitations. Consumers with food allergy then need to be educated to undertake individualized risk assessments in relation to any PAL present.     

Evidence‐based approaches to the application of precautionary allergen labelling: Report from two iFAAM workshops

Food allergy is a major public health concern with avoidance of the trigger food(s) being central to management by the patient. Food information legislation mandates the declaration of allergenic ingredients; however, the labelling of the unintentional presence of allergens is less defined. Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the risk of reaction from the unintended presence of allergens in foods. In its current form, PAL is counterproductive for consumers with food allergies as there is no standardized approach to applying PAL. Foods with a PAL often do not contain the identified food allergen while some products without a PAL contain quantities of common food allergens that are capable of inducing an allergic reaction. Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) was an EU‐funded project that aimed to improve the management of food allergens by the food industry for the benefit of people with food allergies. Within iFAAM, a clinically validated tiered risk assessment approach for food allergens was developed. Two cross‐stakeholder iFAAM workshops were held on 13‐14 December 2016 and 19‐20 April 2018. One of the objectives of these workshops was to develop a proposal to make PAL effective for consumers. This paper describes the outcomes from these workshops. This provides the basis for the development of more informative and transparent labelling that will ultimately improve management and well‐being in consumers with food allergy.     

Food allergen avoidance – the patient's viewpoint

The profile of potentially fatal food allergies has altered in recent years. The vigilance required for allergen avoidance when shopping or eating out depends on information which is often hidden or misleading. Families with allergic children suffer social exclusion and stress, made worse by a serious shortage of specialist patient care. Those who die are usually teenagers and young adults who suffer from severe allergic asthma or anaphylaxis after eating away from the home. A recognised manufacturing standard would endorse businesses seeking to remove the risk of allergen cross-contamination, whilst the integration of allergy into training for caterers and environmental health professionals would influence and inform foodservice businesses.     

Food allergen avoidance in primary prevention of food allergy

Approximately 5–10% of children suffer from allergy to one or more foods. Primary prevention through a hypoallergenic diet may reduce the prevalence of food allergy and associated co-morbidity, such as eczema and urticaria. Breastfeeding has many advantages and should be recommended for all children. Those with a history of atopy in the immediate family are at a higher risk and maternal diet during lactation, avoiding highly allergenic foods, may enhance the benefit. Cow's milk should be strictly avoided, and supplements, if required, should be with a hypoallergenic formula. Delayed introduction of egg, nuts, wheat and fish has also been suggested. Dietary restriction may have nutritional consequences for the mother and child and supervision by a dietician is essential. Maternal diet during pregnancy is not advisable as the benefit is minimal and there may be adverse effects on the foetal nutrition. In high risk infants, a combined approach, where breastfeeding with maternal avoidance of highly allergenic foods, supplemented by extensively hydrolysed formula during the first 6 months of life, in addition to the delayed introduction of solid foods, has been shown to reduce the development of food allergy in infants.     

Surimi and native codfish contain a common allergen identified as a 63-kDa protein

We have compared the allergenicity of codfish and surimi (prepared from codfish) by skin testing, specific IgE-RIA, and leukocyte histamine release (LHR) in six fish-allergic patients. Prick tests were positive for codfish and, to a lesser extent, surimi. The percentages of labeled anti-IgE bound to surimi-Sepharose were 1.55 ± 0.19% and 3-6% with control and patient sera, respectively. Inhibition of the surimi protein-Sepharose IgE-RIA was greatest (80%) at protein concentrations of 13.4 and 408.5 μg/ml for codfish and surimi extract, respectively. The allergenic protein was isolated by gel filtration and subjected to SDS-PAGE. The eluate from codfish contained several proteins ranging from 13 to 63 kDa, while the eluate from surimi contained a single 63-kDa protein. It was concluded that surimi contained a single allergenic protein.
Mata E, Favier C, Moneret-Vautrin DA, Nicolas JP, Han Ching L, Guéant JL. Surimi and native codfish contain a common allergen identified as a 63-kDa protein.     

Food Sensitivity Reported by Patients with Asthma and Hay Fever

Among adult patients with bronchial asthma and/or allergic rhinitis und allergological investigation with skin test, nasal provocation test and RAST, 1129 answered a questionaire regarding food sensitivity (FS). 276 (24%) of the patients reported some kind of allergic symptoms on eating or handling various foods, of which hazel nut, apple and shell fish were the most often mined. Females reported FS most often than males, A correlation was found between birch pollen allergy and FS with nuts, apple, peach, cherry, pear, plum, carrot and new potato. The higher the degree of birch pollen allergy, according to skin test. RAST or provocation test, the higher the frequency of FS.
A correlation was found too between acetylsalicylic acid intolerance and FS with some foods, e.g. nuts, strawberry, almond, green pepper, hip, chocolate, egg, cabbage, milk and wine.
The connection between birch pollen allergy and FS is probably explained by the structural relationship between birth pollen allergen and some allergens of die foodstuffs, whereas the high incidence of FS in acetylsalicylic acid-intolerant patients is probably explained by additives in foods as well as salicylates or benzoates naturally occurring in some food.     

Investigation of the stability of apple allergen extracts

To determine optimal conditions for allergen preservation, we investigated the influence of different stabilizing additives and of storage temperature on the allergen activity of apple protein preparations, obtained by extraction in phosphate buffer or by precipitation in diacetone alcohol and resolubilization in phosphate buffer in the presence or absence of enzyme inhibitors. For this purpose, the extracts were stored for 6 months either in frozen state at −20° C or in lyophilized state at −20° C, 4° C, or room temperature and were characterized by SDS-PAGE, immunoblot, ELISA inhibition, and prick test. The highest stability revealed the extracts that were prepared by precipitation in the organic solvent in the presence of enzyme inhibitors, lyophilized, and stored at −20° C. For storage of extract solutions at 4° C, PBS/glycerol and cysteine/sodium citrate/glycerol were found to be the most effective stabilizing additives.     

Food anaphylaxis

Anaphylaxis is a life-threatening allergic reaction, and food is one of the most common responsible allergens in the outpatient setting. The prevalence of food-induced anaphylaxis has been steadily rising. Education regarding food allergen avoidance is crucial as most of the fatal reactions occurred in those with known food allergies. The lack of a consensus definition for anaphylaxis has made its diagnosis difficult. Symptoms affect multiple organ systems and include pruritus, urticaria, angioedema, vomiting, diarrhoea, abdominal cramps, respiratory difficulty, wheezing, hypotension, and shock. Prompt recognition of anaphylaxis is essential as delayed treatment has been associated with fatalities. Although epinephrine is accepted as the treatment of choice, timely administration does not always occur, partly due to a lack of awareness of the diagnostic criteria. Several novel tools are currently being investigated, which will potentially aid in the diagnosis and treatment of food-induced anaphylaxis.     

Boletus edulis: a digestion-resistant allergen may be relevant for food allergy

BACKGROUND: Fungal components can cause allergic symptoms either through inhalation, ingestion or contact. Whereas respiratory allergy is thought to be induced by spores, allergic reactions following ingestion are attributed to other parts of the mushroom. Reports of food-related allergic reactions due to the edible mushroom Boletus edulis have occasionally been reported. OBJECTIVE: The aim of the study was to investigate whether separate allergens may be detected in alimentary allergy to Boletus edulis. METHODS: Sera of two subjects, one with recurrent anaphylaxis and the other with a predominantly oral allergy syndrome following ingestion of Boletus edulis, have been analysed by a time-course digestion assay using simulated gastric fluid and by SDS-PAGE immunoblotting. Sera of four Boletus edulis skin prick test-negative subjects and all without clinical symptoms to ingested Boletus edulis served as controls. RESULTS: In lyophilized Boletus edulis extract, at least four water-soluble proteins were detected, the most reactive at 55 kDa and at 80 kDa. Following the time-course digestion assay, IgE binding was found to a 75-kDa protein, but only if the sera of the subject with recurrent anaphylaxis was used. CONCLUSION: The data indicate that Boletus edulis can cause an IgE-mediated food allergy due to a digestion-stabile protein at 75 kDa. No IgE immune response to this protein was detected in the serum of a subject with respiratory allergy and oral allergy syndrome to Boletus edulis nor in control sera.     

Enhancement of hazelnut extract for IgE testing by recombinant allergen spiking

BACKGROUND: Hazelnuts are a common cause of food allergic reactions. Most hazelnut allergic individuals in central and northern Europe are sensitized to Cor a 1, a member of the PR-10 protein family, while the lipid transfer protein Cor a 8 acts as a major allergen in the south of Europe. Other allergens, including profilin and seed storage proteins, may be important in subgroups of patients. Reliable detection of specific IgE in the clinical diagnosis of food allergy requires allergen reagents with a sufficient representation of all relevant allergen components. Some reported observations suggest that natural hazelnut extract may not be fully adequate in this respect. METHODS: The capacity of immobilized natural hazelnut extract to bind Cor a 1-, Cor a 2- and Cor a 8-specific IgE and IgG antibodies was investigated by serum adsorption and extract dilution experiments and by the use of allergen specific rabbit antisera. All measurements were performed with the ImmunoCAP assay platform. RESULTS: The experimental results revealed an incomplete capacity of immobilized hazelnut extract to capture IgE antibodies directed to the major allergen Cor a 1. Spiking of hazelnut extract with recombinant Cor a 1.04 prior to solid phase coupling gave rise to significantly enhanced IgE antibody binding from Cor a 1 reactive sera. The spiking did not negatively affect the measurement of IgE to extract components other than Cor a 1. CONCLUSION: A hazelnut allergen reagent with enhanced IgE detection capacity can be generated by supplementing the natural food extract with recombinant Cor a 1.04.     

A 17-kDa allergen detected in pine nuts

BACKGROUND: Few cases of allergy to pine nuts have been described. We report a case of anaphylactic reaction to pine nuts. The patient needed to be treated in the emergency room due to a systemic reaction immediately after eating pine nuts. METHODS: The patient was studied by prick tests and prick by prick tests. Specific IgE was measured by CAP and by SDS-PAGE/immunoblotting by a diffusion method. RESULTS: The patient showed positive prick by prick tests to pine nuts (12 mm of maximum wheal diameter). Specific IgE was positive (0.79 kU/l). The patient's serum recognized several proteins by immunoblot. However, a 17-kDa allergen band was detected with high intensity. This protein was found to be sensitive to reducing agents, losing its IgE-binding properties after reduction. CONCLUSIONS: The patient presented an IgE-mediated reaction and detected a 17-kDa protein from pine nuts not previously described.     

IgE-binding and cross-reactivity of a new 41 kDa allergen of codfish

Background:   A 41-kDa IgE-reactive protein (p41) was purified from raw cod extract. This protein is homologous to an aldehyde phosphate dehydrogenase (APDH). The present study aims to evaluate the IgE-binding and the cross-reactivity of this protein in 13 patients allergic to codfish.
Methods:   IgE binding of sera from 13 patients allergic to codfish was tested by Sepharose RIA and by Western blot.
Results:   Among the 13 patients, only 4 had specific IgE to APDH detected by APDH-Sepharose RIA. The two patients who had the highest level of specific IgE to human APDH also had a class 5–6 CAP-RAST IgE level to codfish, but two other patients with a class 5 had a negative APDH-Sepharose IgE-RIA. Relative content of APDH was higher in extracts of commercial nonfrozen fish, compared to pre rigor mortis , post rigor mortis and frozen commercial codfish. A high homology of codfish APDH was found with the corresponding human enzyme. A significant inhibition of APDH-Sepharose by human and, to a lesser extent, by rabbit APDH was observed. Western blot of APDH codfish extract showed two bands at 41 and 36 kDa, respectively.
Conclusions:   We have characterized a new allergen from codfish, which had a high level of homology in different species. The p41 relative content of extracts from nonfrozen codfish was higher than in the other samples assessed.