Sensitization to peanut, egg or pets is associated with skin barrier dysfunction in children with atopic dermatitis.

BACKGROUND: Children with atopic dermatitis (AD) are often sensitized to food and aeroallergens, but sensitization patterns have not been analysed with biologic measures of disease pathogenicity. OBJECTIVE: We sought to define allergen sensitization grouping(s) using unbiased machine learning and determine their associations with skin filaggrin (FLG) and transepidermal water loss (TEWL) (assesses skin barrier integrity), S100A8 and S100A9 expression (assesses skin inflammation) and AD severity. METHODS: We studied 400 children with AD in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort to identify groupings of food and aeroallergen sensitizations. MPAACH is a paediatric AD cohort, aged 1-2, recruited through hospital/community settings between 2016 and 2018. We analysed these groupings' associations with AD biomarkers: skin FLG, S100A8 and S100A9 expression, total IgE, TEWL and AD severity. RESULTS: An unbiased machine learning approach revealed five allergen clusters. The most common cluster (N = 131), SPTPEP, had sensitization to peanut, egg and/or pets. Three low prevalence clusters, which included children with allergen sensitization other than peanut, egg or pets, were combined into SPTOther . SPTNEG included children with no sensitization(s). SPTPEP children had higher median non-lesional TEWL (16.9 g/m2 /h) and IgE (90 kU/L) compared with SPTOTHER (8.8 g/m2 /h and 24 kU/L; p = .01 and p < .001) and SPTNEG (9 g/m2 /h and 26 kU/L; p = .003 and p < .001). SPTPEP children had lower median lesional (0.70) and non-lesional (1.09) FLG expression compared with SPTOTHER (lesional: 0.9; p = .047, non-lesional: 1.78; p = .01) and SPTNEG (lesional: 1.47; p < .001, non-lesional: 2.21; p < .001). There were no differences among groupings in S100A8 or S100A9 expression. CONCLUSIONS AND CLINICAL RELEVANCE: In this largely clinic-based cohort of young children with AD, allergic sensitization to peanut, egg, cat or dog was associated with more severe disease and skin barrier function but not markers of cutaneous inflammation. These data need replicating in a population-based cohort but may have important implications for understanding the interaction between AD and allergic sensitization.

Oesophageal eosinophilia accompanies food allergy to hen egg white protein in young pigs.

BACKGROUND: Esophagitis with eosinophilia, inflammation, and fibrosis represent a chronic condition in humans with food allergies. OBJECTIVE: In this investigation, we asked whether esophagitis with an eosinophilic component is observed in young pigs rendered allergic to hen egg white protein (HEWP). METHODS: Food allergy was induced in young pigs using two protocols. In one protocol, sensitized pigs were challenged by gavage with a single dose of HEWP. Clinical signs were monitored for 24 hours, and then, gastrointestinal (GI) tissues were collected for histological examination. The phenotype of circulating, ovalbumin (OVA)-specific T cells also was examined in HEWP challenged animals. In the second protocol, sensitized animals were fed HEWP for 28 days. Animals were then examined by endoscopy and gastrointestinal tissues collected for histological examination. RESULTS: In pigs challenged by gavage with HEWP, clinical signs were noted in 5/6 pigs including diarrhoea, emesis, and skin rash. Clinical signs were not seen in any control group. Histological analysis revealed significant levels of oesophageal eosinophilic infiltration (P < .05) in 4/6 of these animals, with two also displaying eosinophilic infiltration in the stomach. Eosinophils were not increased in ileum or colon samples. Increased numbers of circulating, OVA-specific CD4+ T cells also were observed in pigs that received HEWP by gavage. In the group of animals fed HEWP, endoscopy revealed clinical signs of esophagitis including oedema, granularity, white spots, and furrowing, while histology revealed oedema, immune cell infiltration, and basal zone hyperplasia. CONCLUSIONS AND CLINICAL RELEVANCE: Food allergy in the pig can be associated with esophagitis based on histological and endoscopic findings, including eosinophilic infiltration. The young pig may, therefore, be a useful large animal model for the study of eosinophilic esophagitis in humans.

Food-induced anaphylaxis in infancy compared to preschool age: A retrospective analysis.

OBJECTIVE: Little is known regarding food anaphylaxis in infancy. We aimed to describe specificities of food anaphylaxis in infants (≤12 months) as compared to preschool children (1-6 years). METHODS: We conducted a retrospective study of all food anaphylaxis cases recorded by the Allergy Vigilance Network from 2002 to 2018, in preschool children focusing on infants. RESULTS: Of 1951 food anaphylaxis reactions, 61 (3%) occurred in infants and 386 (20%) in preschool children. Two infants had two anaphylaxis reactions; thus, we analyzed data among 59 infants (male: 51%; mean age: 6 months [SD: 2.9]); 31% had a history of atopic dermatitis, 11% of previous food allergy. The main food allergens were cow's milk (59%), hen's egg (20%), wheat (7%) and peanut (3%) in infants as compared with peanut (27%) and cashew (23%) in preschool children. Anaphylaxis occurred in 28/61 (46%) cases at the first cow's milk intake after breastfeeding discontinuation. Clinical manifestations were mainly mucocutaneous (79%), gastrointestinal (49%), respiratory (48%) and cardiovascular (21%); 25% of infants received adrenaline. Hives, hypotension and neurologic symptoms were more likely to be reported in infants than in preschool children (P = .02; P = .004; P = .002, respectively). Antihistamines and corticosteroids were more often prescribed in preschool children than in infants (P = .005; P = .025, respectively). CONCLUSION: Our study found that in infants presenting with their first food allergy, in a setting with a high rate of infant formula use, the most predominant trigger was cow's milk. As compared to older preschool children, hives, hypotonia and hypotension were more likely to be reported in infants. We believe that this represents a distinct food anaphylaxis phenotype that can further support developing the clinical anaphylaxis criteria in infants.

Food allergy to previously tolerated foods: Course and patient characteristics.

BACKGROUND: The acquisition of food allergy (FA) to previously safely consumed basic food proteins is an unusual presentation of immunoglobulin E (IgE)-mediated allergic disease. OBJECTIVE: We sought to characterize patients who developed FA to previously tolerated foods (FA-PTF), including underlying reasons for and length of elimination diet of previously tolerated foods. METHODS: Patients (n = 30) with complaints consistent with FA to foods previously consumed safely were evaluated. Clinical history was obtained, and skin prick testing and graded oral food challenges (OFC) were performed. One fatal case of FA-PTF was reported by a physician. RESULTS: Twenty-two of 30 patients (ages 1.2-50 years) were diagnosed with FA-PTF by OFC to milk (n = 17), egg (n = 2), and peanuts (n = 3). One additional patient with FA-PTF had a fatal reaction to milk. Anaphylactic reactions were reported in 12 of these 23 FA-PT patients (52%); 8 experienced multiple episodes. Atopic dermatitis was diagnosed in 52% (12/23) of patients, 8 of 12 as severe; overall, 18 of 23 (78%) of patients had marked personal atopic background. Sixteen patients (70%) initiated an elimination diet, 12 of whom did so on advice from a health care provider, before the appearance of allergic symptoms. However, in 4 patients with FA-PTF, reactivity to the food protein emerged during uninterrupted consumption. CONCLUSION: Food allergy to previously tolerated foods primarily appears after an elimination diet in atopic patients. Anaphylactic reactions are common. Health care providers should consider these risks before recommending elimination diet of tolerated foods.

Caregiver and expecting caregiver support for early peanut introduction guidelines.

BACKGROUND: Recent guidelines recommend early peanut introduction (EPI) beginning around 4 to 6 months of age in infants with severe eczema and/or egg allergy and around 6 months for all other infants. Caregiver preferences for such practices are unknown. OBJECTIVE: To determine levels of support for early allergenic solid food recommendations among new and expecting caregivers of infants at risk for peanut allergy. METHODS: We explored preferences for EPI and in-office allergy risk assessment (IRA) through a nationally representative survey of expecting (n = 1,000) and new caregivers of infants younger than 1 year (n = 1,000). RESULTS: Among a primarily female (99.7%), married (80.3%), and white (74.4%) sample, 29% had no or vague awareness of the new guidelines, 61% had no or minimal concern for their child developing food allergy, but 54% felt timing of food introduction has moderate to strong importance for developing food allergy. Only 31% expressed willingness for EPI before or around 6 months of age, with 40% reporting willingness to introduce peanut after 11 months of age, similar to tree nuts and seafood. However, 60% reported willingness to introduce egg before 8 months of age. A total of 51% and 56.8% were unwilling to allow IRA methods, such as skin testing and oral challenge, before 11 months of age, respectively. Odds of willingness to delay peanut introduction (odds ratio, 0.79; 95% confidence interval, 0.65-0.96) and undergo challenge (odds ratio, 0.67; 95% confidence interval, 0.54-0.82) after 6 months of age were lower among expecting caregivers. CONCLUSION: Among new and expecting caregivers, there is poor current willingness and questionable support for early allergenic solid food recommendations, including IRA before introduction. Willingness was better among expecting vs current caregivers. These trends underscore a need for broader formal implementation planning to facilitate early allergen introduction and maximize its preventive benefits.

Safety of live attenuated influenza vaccine in atopic children with egg allergy.

BACKGROUND: Live attenuated influenza vaccine (LAIV) is an intranasal vaccine recently incorporated into the United Kingdom immunization schedule. However, it contains egg protein and, in the absence of safety data, is contraindicated in patients with egg allergy. Furthermore, North American guidelines recommend against its use in asthmatic children. OBJECTIVE: We sought to assess the safety of LAIV in children with egg allergy. METHODS: We performed a prospective, multicenter, open-label, phase IV intervention study involving 11 secondary/tertiary centers in the United Kingdom. Children with egg allergy (defined as a convincing clinical reaction to egg within the past 12 months and/or >95% likelihood of clinical egg allergy as per published criteria) were recruited. LAIV was administered under medical supervision, with observation for 1 hour and telephone follow-up 72 hours later. RESULTS: Four hundred thirty-three doses were administered to 282 children with egg allergy (median, 4.9 years; range, 2-17 years); 115 (41%) had experienced prior anaphylaxis to egg. A physician's diagnosis of asthma/recurrent wheezing was noted in 67%, and 51% were receiving regular preventer therapy. There were no systemic allergic reactions (upper 95% CI for population, 1.3%). Eight children experienced mild self-limiting symptoms, which might have been due an IgE-mediated allergic reaction. Twenty-six (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 with parent-reported wheeze. None of these episodes required medical intervention beyond routine treatment. CONCLUSIONS: In contrast to current recommendations, LAIV appears to be safe for use in children with egg allergy. Furthermore, the vaccine appears to be well tolerated in children with a diagnosis of asthma or recurrent wheeze.

Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis.

BACKGROUND: The onset of eosinophilic esophagitis (EoE) after oral immunotherapy (OIT) has been repeatedly described in patients with immunoglobulin E (IgE)-mediated food allergy in recent years, but the relation between the 2 conditions has not been fully assessed and quantified. OBJECTIVE: To provide a systematic review of the evidence for an association between OIT and EoE. METHODS: Electronic searches were performed with keywords relating to EoE and OIT in the MEDLINE, EMBASE, and SCOPUS databases. Summary estimates were calculated. A fixed-effects model was used depending on heterogeneity (I(2)). Risk of publication bias was assessed by funnel plot analysis and the Egger test. RESULTS: The search yielded 118 documents, 15 of which were included in the quantitative summary. Most reported information came from children undergoing peanut, milk, and egg OIT. Significant publication bias in favor of studies reporting the development of EoE after OIT was documented. The overall prevalence of EoE after OIT was 2.7% (95% confidence interval 1.7%-4.0%, I(2) = 0%). Differences between medium-to high-quality studies and those of low quality were documented (3.5% vs 2.5%, respectively). EoE often resolved after OIT discontinuation; histologic remission of EoE achieved after allergen immunotherapy also was documented in 2 patients whose topical fluticasone treatment failed. CONCLUSION: New onset of EoE after OIT occurs in up to 2.7% of patients with IgE-mediated food allergy undergoing this treatment strategy. The limited data on the utility of allergen immunotherapy as a therapy for EoE prevent a recommendation for this treatment option.

Outcome of oral provocation test in egg-sensitive children receiving semi-fat hard cheese Grana Padano PDO (protected designation of origin) containing, or not, lysozyme.

PURPOSE: Lysozyme, obtained from egg white, is a potential food allergen used in the dairy industry to prevent late blowing of the loaf caused by the outgrowth of clostridial spores (Cl. butyricum and Cl. tyrobutyricum) during cheese aging. The aim of this study was to evaluate the possible correlation between egg protein allergy in pediatric age and sensitization to egg lysozyme, used for the preparation of Grana Padano cheese. METHODS: The tolerability of Grana Padano cheese has been evaluated in pediatric patients allergic to egg proteins through an oral provocation test with increasing amounts of cheese containing, or not, lysozyme at 12 and 24 months of aging. RESULTS: When lysozyme-sensitized children received 12-months aged and lysozyme-containing cheese, several immediate and late adverse reactions such as itching, abdominal pain, vomiting, nausea, dermatitis, rhinitis, bronchial asthma, urticaria, and angioedema were seen in 5 out of 21 subjects; only 1 out of 21 children showed an adverse reaction after challenge with 24-months-ripened lysozyme-containing cheese. CONCLUSIONS: There is a possible relationship between the severity of allergic reactions and the lysozyme-specific IgE level in blood. In particular vomiting, hypotension, and abdominal pain were present when IgE level was higher than 7 kU/L. A ripening time of 24 months may reduce allergy problems when lysozyme-containing cheese is given to sensitized subjects, probably due to the hydrolysis of antigenic epitopes during aging.

Oral food challenge: safety, adherence to guidelines and predictive value of skin prick testing.

BACKGROUND: The diagnostic gold standard of food allergy is the oral food challenge (OFC). Data on severe reactions and drug use during OFC are scarce. Our aims were (i) to investigate the prevalence and spectrum of reactions' severity during OFC and to assess drug use and epinephrine use in anaphylaxis due to OFC; (ii) to investigate the predictive value of the skin prick test wheal size for the outcome of OFCs. METHODS: A retrospective charts review of children undergoing OFC at three Allergy Centres between January 2007 and December 2008 was performed. RESULTS: A total of 544 OFCs were analysed. Most frequently involved foods were egg, milk and wheat. 254/526 (48.3%) were positive. 167 (65.7%) were defined mild reactions, 81 (31.9%) multiorgan reactions and 6 (2.4%) anaphylaxis. No patients had cardiovascular symptoms. Data on treatments were available in 98.8% OFCs. In half of them antihistamines were used vs. 10% cases in which steroids were preferred. Six children (2.4%) were treated with Epinephrine inhalation, 5 (2%) with beta-2 inhalation, 8 (3.1%) with steroid inhalation. One child was treated with IM Epinephrine + IV fluids. Skin prick tests predictive cut-off were 9 mm for albumen, 7 for yolk, 13 for fresh albumen, 10 for α-lactalbumin, seven for casein, eight for ß-lactoglobulin, 20 for cow's milk and 10 for fresh cow's milk. CONCLUSION: OFCs performed in controlled settings by expert Allergists are safe. Consideration needs to be given as to whether the Anaphylaxis' Guideline need to be modified when applied in treating patients undergoing OFC.

Clinical thresholds to egg, hazelnut, milk and peanut: results from a single-center study using standardized challenges.

BACKGROUND: Large studies of individual thresholds and risk profiles for foods are sparse. Previous reports indicate that thresholds adjusted for the protein content in foods would be comparable. OBJECTIVE: To establish and compare clinical threshold values for egg, hazelnut, milk and peanut, and correlating them to severity of symptoms. METHODS: Seven hundred eighty-one challenges were performed in 487 patients (age range, 0.5-73.5 years). Using interval censoring survival analysis, the dose distribution of thresholds was fitted to a log-normal function. Symptom score was correlated to thresholds. RESULTS: Based on the 405 challenges resulting in objective signs, similar distribution of thresholds for hazelnut, milk, and peanut challenges were found, whereas individuals with egg allergy were bimodally distributed with a high or a low threshold. Eliciting dose in 10% (95% confidence interval) was 42.9 (24-76.8) mg whole eggs, 133.8 (95.9-186.6) mg whole hazelnut, 106.5 (59.7-190.6) mg roasted peanut, and 2.9 (1.5-5.4) mL milk. Adults showed more severe symptoms and signs than children, and peanut caused more severe reactions than the 3 other foods. CONCLUSION: Thresholds for the different foods were not comparable, and eliciting dose for the 4 foods differed, even if adjusted for protein content. Increasing age but not a low threshold dose is associated with severe symptoms on challenge. Peanuts elicit more severe reactions than the other foods.

Hen egg hair mask-induced food allergy: a case report.

We report the case of a 46-year-old woman who treated her hair with a homemade egg-white based mask. After one year of weekly applications, the ingestion of egg triggered rhinitis, choking and systemic urticaria. Though the breakdown of oral tolerance to egg has been reported elsewhere in the literature, to the best of our knowledge, this is the first case of hair mask-induced allergy.

Egg white specific IgE levels in serum as clinical reactivity predictors in the course of egg allergy follow-up.

It is thought that the natural evolution of egg allergy has a good tolerance prognosis. However, there are few follow-up studies that determine the exact probability of tolerance. The aim of this study was to determine the likelihood that children younger than 2,5 years of age with allergy to egg would eventually have tolerance to it and to analyze if monitoring egg white-specific IgE level over time could be used as a predictor for determining when patients develop clinical tolerance. We performed a retrospective study of our last 42 patients diagnosed with egg allergy. Annual follow-up comprised prick testing, specific IgE (sIgE) and provocation testing with egg white (EW), allowing the prediction of tolerance at that timepoint with a probability of >or=95%. Median survival time was 48 months. The mean initial and final levels of EW sIgE were lower in the patients that reached tolerance (p<0.05). EW sIgE levels of 1.52, 1.35, and 2.59 KUA/l, respectively predicted clinical reactivity (PPV > 95%) at the different follow-up timepoints analyzed (25-36, 37-48 and 49-60 months. Quantification of egg white specific IgE levels is a useful test for diagnosing symptomatic allergy to egg white in the pediatric population and could eliminate the need to perform oral challenges tests in a significant number of children.

Results of the oral egg-challenge test performed on two different groups of children. One group with a history, suggestive of allergic reaction with egg intake and the other group sensitised to hen's egg without previous egg intake.

INTRODUCTION: Egg allergy is an adverse immune-system reaction of an IgE-mediated type, which can happen in children after egg intake and several times after their first egg intake. OBJECTIVES: Compare the results of the oral egg-challenge test in two groups of egg-sensitised children, with and without prior intake. PATIENTS AND METHODS: Retrospective study of two egg-sensitised groups (72 subjects). Group 1: 22 children without prior egg-intake. Group 2: 50 children with a clinical history of adverse reactions after egg intake. Skin prick tests, egg-white specific IgE (sIgE) and yolk specific IgE, were performed on all children. The oral egg-challenge tests were performed after a period of egg-avoidance diet and when egg-white specific IgE levels were lower than 1.5K U/L. RESULTS: 31.8% of the children in Group 1 did not tolerate egg-intake whereas 38% of the children in Group 2 did not tolerate egg-intake. Egg-avoidance periods lasted 19.5 and 18 months, respectively. Egg-white specific IgE levels went down in both groups after an egg-avoidance diet. No statistically significant differences were found between the groups and the positivity of oral egg-challenge test. CONCLUSIONS: No statistically significant differences were found in the behaviour of the two groups studied. Given the high risk of adverse reactions, it was recommended that any egg-introduction tests were to be performed in a hospital environment on the children who were sensitised to hen's egg (including children without prior egg intake).

Rush specific oral tolerance induction in school-age children with severe egg allergy: one year follow up.

BACKGROUND: At present, the only treatment for food allergy is to avoid the allergy-causing food. Some trials of specific oral tolerance induction (SOTI) have been carried out, but the rate of tolerance induction was low despite long treatment periods, at least 3 months to several years. A new type of treatment is long desired. The objectives of this study are to perform our rush SOTI for school-age patients with severe egg allergy, and to evaluate the safety and efficacy of this method for one year. METHODS: Six school-age children (7-12 years of age) with severe IgE-mediated egg allergy confirmed by double-blind, placebo-controlled food challenge (DBPCFC) underwent rush SOTI, in which patients ingested increasing doses of egg several times every day. After rush SOTI, patients ingested the maintenance dose of egg at least twice a week. RESULTS: In DBPCFC, the median threshold dose of egg white inducing allergic reactions was 0.152 g (0.012-0.360 g). All subjects acquired tolerance to more than one whole egg (60 g). It took only 12 days (9-18 days). None experienced any serious reaction. We observed a decrease in IL-10 and an increase in TGF-beta1 at 6 months and a decrease in egg-specific IgE and an increase in egg white-specific IgG4 at 12 months after rush SOTI in blood. All subjects have been able to ingest more than one whole egg ever since. CONCLUSIONS: Our rush SOTI is a safe and effective treatment for severe food allergy since only a few weeks are needed to acquire tolerance. It would replace allergen avoidance as the treatment for food allergy.

Lipocalin-type prostaglandin D synthase and egg white cystatin react with IgE antibodies from children with egg allergy.

BACKGROUND: Ovalbumin, ovomucoid, ovotransferrin, lysozyme, and ovomucin are known to be major allergens found in egg white. Egg white protein is composed of over 30 proteins; many of which have neither been identified nor their allergenicities characterized. This study set out to analyze whether unknown proteins that bind to IgE antibodies in serum from patients with egg allergy exist in egg white. METHODS: Diluted egg white proteins were separated by 2-dimensional (2-D) gel electrophoresis. Immunolabeling was performed on individual patient sera from 19 child patients with egg white allergy and 11 negative control subjects. Spots of egg white proteins that bound to the patients' IgE were identified by mass spectrometry-based proteomics. RESULTS: Egg white proteins were separated into 63 spots. Twenty-five of the 63 reacted with egg allergy patients' sera, and 10 of the 25 reactive spots showed IgE-reactivity to controls as well. Specific bindings to the IgE from egg allergy patients were found in 15 spots; one of which was confirmed as ovotransferrin. Among the other 14 protein spots, egg white cystatin and lipocalin-type prostaglandin D synthase (L-PGDS) were newly identified proteins that reacted with IgE in patients with egg allergy. CONCLUSIONS: We demonstrated that L-PGDS and cystatin reacted with serum IgE in patients with egg allergy. Our proteomics-based analysis in egg white gives a comprehensive map of proteins bound with IgE and should assist in enabling more accurate diagnoses and recommendations of desensitizing treatments for individual patients.

Egg allergy and influenza vaccination.

Many egg-allergic patients are unnecessarily restricted from receiving the influenza vaccine. Patients with suspected egg allergy who require seasonal or H1N1 influenza vaccination can pose a significant challenge and should be appropriately evaluated by an allergist/immunologist. In most cases, if the benefits are felt to outweigh the risks, precautionary measures are available that can enhance safe vaccine administration. A case of influenza vaccine management in a child with egg allergy is presented. Clinical characteristics, diagnostic testing, case management, and natural history are reviewed. Clinical Pearls and Pitfalls include: (1) Batch-to-batch variability of egg content in extant influenza vaccines necessitates an informed and cautious approach to vaccination of an egg-allergic individual. (2) Due to denaturation of some egg proteins through heating, tolerance of "baked egg" products may not predict tolerance of "native egg" proteins present in the influenza vaccine. (3) Intradermal skin testing with influenza vaccine diluted 1:10 may be irritating to the skin and result in false positive results. (4) If skin test to the vaccine is positive, vaccination may still be cautiously administered, if necessary, in a graded-dose protocol, as presented herein. (5) Most patients with egg allergy are likely to develop egg tolerance by late childhood.

The natural history and prognostic factors of egg allergy in Korean infants with atopic dermatitis.

The aim of this study was to understand the natural course of egg allergy and to identify the prognostic factors for tolerance. A retrospective study that included 106 children with atopic dermatitis and egg allergy diagnosed at less than 2 years of age was conducted using medical records and parental telephone interviews. Tolerance was defined as the absence of an allergic reaction in response to the parental introduction of cooked eggs to the diet of children whose egg white specific IgE level had decreased to less than 1.5 kU(A)/l. The median age of tolerance to egg allergy was 4 years. Kaplan-Meier analysis predicted that 41% of children had developed tolerance to egg allergy by age 3, while 60% of children had developed tolerance by age 5. The age at the diagnosis of egg allergy was the only significant prognostic factor of egg allergy tolerance identified by the Cox proportional regression model.

Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment.

An animal model for food allergy is needed to assess genetically modified food crops for potential allergenicity. The ideal model must produce allergic antibody (IgE) to proteins differentially according to known allergenicity before being used to accurately identify potential allergens among novel proteins. The oral route is the most relevant for exposure to food antigens, and a protein's stability to digestion is a current risk assessment tool based on this natural route. However, normal laboratory animals do not mount allergic responses to proteins administered orally due to oral tolerance, an immunologic mechanism which specifically suppresses IgE. To circumvent oral tolerance and evoke differential IgE responses to a panel of allergenic and nonallergenic food extracts, female C3H/HeJ mice were exposed subcutaneously or orally with cholera toxin as an adjuvant. All foods elicited IgE by the subcutaneous route. Oral exposure, however, resulted in IgE to allergens (peanut, Brazil nut, and egg white) but not to nonallergens (spinach and turkey), provided that the dose and exposures were limited. Additionally, in vitro digestibility assays demonstrated the presence of digestion-stable proteins in the allergenic food extracts but not in the nonallergenic foods. Our results suggest that the subcutaneous route is inadequate to distinguish allergens from nonallergens, but oral exposure under the appropriate experimental conditions will result in differential allergic responses in accordance with known allergenicity. Moreover, those foods containing digestion-resistant proteins provoke allergic responses in this model, supporting the current use of pepsin resistance in the decision tree for potential allergenicity assessment.