Cause Of Food-induced Anaphylaxis Research Articles

Genomics of Shrimp Allergens and Beyond.

Allergy to shellfishes, including mollusks and crustaceans, is a growing health concern worldwide. Crustacean shellfish is one of the "Big Eight" allergens designated by the U.S. Food and Drug Administration and is the major cause of food-induced anaphylaxis. Shrimp is one of the most consumed crustaceans triggering immunoglobulin E (IgE)-mediated allergic reactions. Over the past decades, the allergen repertoire of shrimp has been unveiled based on conventional immunodetection methods. With the availability of genomic data for penaeid shrimp and other technological advancements like transcriptomic approaches, new shrimp allergens have been identified and directed new insights into their expression levels, cross-reactivity, and functional impact. In this review paper, we summarize the current knowledge on shrimp allergens, as well as allergens from other crustaceans and mollusks. Specific emphasis is put on the genomic information of the shrimp allergens, their protein characteristics, and cross-reactivity among shrimp and other organisms.

Closed-tube saltatory rolling circle amplification with hydroxynaphthol blue for visual on-site detection of peanut as an allergenic food

Peanut allergy as one of the major causes of food-induced anaphylaxis is usually life-threatening for specific individuals. Nowadays, the effective remedy is avoidance of consuming allergen-containing food, urging monitoring the presence of peanut in foods. Herein, we proposed a closed-tube saltatory rolling circle amplification (SRCA) assay with hydroxynaphthol blue (HNB) for visual on-site detection of peanut allergen, displaying highly specificity for Ara h 1-encoding gene. The results can be discriminated by naked eye without opening the tube, averting costly sophisticated apparatus and reducing the risk of cross-contamination. The assay was 1000-, 100- and 10-fold more sensitive than PCR, LAMP and SRCA, respectively. The relative limit of detection is 0.01% in a binary mixture. The relative sensitivity, specificity and accuracy of this method were 100%, 97.50% and 98.67%, respectively. Thus, the visual closed-tube HNB-SRCA assay with superiorities of easy-to-perform, cost-effective and user-friendly has excellent potential for on-site application of food allergy.

Predictor of buckwheat allergy in children based on challenge test results: a retrospective observational study in Japan.

Background. Buckwheat (BW) is a major food allergen and one of the leading causes of food-induced anaphylaxis in Japan. The standard method of diagnosing food allergy is the oral food challenge (OFC). The BW-specific IgE (BW-sIgE) value is used to assess BW allergy but its utility is limited. Aim. The aim of the present study was to identify factors with predictive value for the diagnosis of BW allergy using the OFC. Methods. We evaluated 37 patients who were classified into the positive or negative group according to their OFC results. Results. Ten patients (27.0%) showed objective or persistent, moderate, subjective symptoms during the OFC. The positive group had a significantly higher BW-sIgE/total IgE ratio than the negative group (p less than 0.001), but the total IgE (p = 0.139) and BW-sIgE (p = 0.130) did not differ significantly. Receiver operator characteristic (ROC) analysis showed that the BW-sIgE/total IgE ratio had a larger area under the curve (AUC, 0.885) than BW-sIgE (AUC, 0.667). The statistically optimal cut-off was 0.0058 for the BW-sIgE/total IgE ratio, which corresponded to a clinical sensitivity and specificity of 90.0% and 81.5%, respectively. Conclusions. BW-sIgE/total IgE ratio may be more useful predictor of BW OFC results than BWs-IgE.

Characteristics and Laboratory Findings of Food-Induced Anaphylaxis in Children: Study in an Asian Developing Country

Introduction: Food allergy is the major cause of pediatric anaphylaxis. Characteristics and triggers may be different in different geographical regions. Studies focusing on food-induced anaphylaxis (FIA) in Asian developing countries are limited. Our study aimed to study characteristics of FIA in a tertiary care center in an Asian developing country. Methods: Retrospective review of pediatric anaphylaxis admission and outpatient visit at a tertiary care hospital in Bangkok, Thailand during 2008–2018 was performed. Data regarding clinical presentation, place reaction occurred, time of onset, investigations (serum tryptase, specific immunoglobulin E, and skin test), treatment, and follow-up periods were collected. Results: One hundred seventy-four anaphylaxis admission records of which 61 episodes of FIA were retrieved. Data from outpatients visit consisted of 17 patients. Most patients were male (76.7%). The median age was 7.1 years (interquartile range 1.9–12.4). The major causes of FIA were shrimp/shellfish (37%), wheat (15.1%), and cow’s milk (11%). Food causing anaphylaxis varied according to age-group: infants had anaphylactic reactions to egg, wheat, and cow’s milk, preschools to wheat and peanut, and older children to shrimp/shellfish. Cutaneous manifestations occurred in all patients, followed by lower respiratory tract symptoms (83.6%) and gastrointestinal symptoms (50.8%). There was no biphasic anaphylaxis reported. Elevated serum tryptase was found in only 4 patients (7%). Conclusion: Recognizing characteristics of pediatric FIA is crucial. The common causes of FIA in our study in Asian children were egg in infants, wheat and peanut in preschool children, and shrimp/shellfish in school-age children and adolescents. Skin manifestation presented in all patients with FIA.

Immunonutrition for Pediatric Patients With Cow's Milk Allergy: How Early Interventions Could Impact Long-Term Outcomes.

Cow's milk allergy (CMA) is one of the most common food allergies and one of the main causes of food-induced anaphylaxis in the pediatric age. Moreover, up to 45% of CMA children develop other atopic manifestations later in life, a phenomenon commonly named atopic march. Thus, CMA imposes a significant cost to health care systems as well as to families, and has emerged as one of the most expensive allergic diseases. The immunonutrition strategy builds its foundation on the ability of selected dietary factors to modulate immune system development and function. Recent studies highlighted the potential of immunonutrition in the management of CMA. This review is focused on the mechanisms and long-term clinical outcomes of the immunonutrition approach in children with CMA.

A novel case discussion of pediatric lipid transfer protein syndrome

Lipid transfer proteins (LTPs) are allergens widely found in plants and plant-derived foods.1,2 Lipid transfer protein syndrome occurs in individuals sensitized to LTPs. Lipid transfer protein syndrome is a significant cause of food-induced anaphylaxis as well as food-dependent exercise-induced anaphylaxis.3 Lipid transfer proteins represent dominant proteins that cause allergic reactions to fruits, nuts, and vegetables in adults and children from the Mediterranean basin; yet, whereas LTP syndrome is common in Mediterranean countries, it is rare in birch endemic areas (ie, northern Europe).

Tree Nuts Anaphylaxis in Preschool Age Children.

Introduction. The incidence of food-induced anaphylaxis (FIA) is increasing in young children. Although the commonest culprits are cow's milk and egg, FIA to tree nuts (TNs) have been increasing. Objective. Characterization of children referred to our allergy department due to TNs-induced anaphylaxis (TNs-FIA) during preschool age. Materials and methods. We have retrospectively included 25 children with clinical history of preschool TNs-FIA, proven by allergological work-up. TNs sensitization was assessed by skin prick tests and/or specific IgE. Results. The mean age of the first anaphylactic episode was 3.1±1.2 years. The majority (92%) had an allergic disease (52% asthma). The implicated TNs were cashew (11 children), walnut (8), pine nut (5), hazelnut (2) and almond (1). The reaction occurred after the first known ingestion in 68%. In 92%, symptoms appeared within 30 minutes after exposure. The most frequent clinical symptoms were mucocutaneous (96%), respiratory (80%) and gastrointestinal (52%). Twenty-one children were admitted to the emergency department, although only 48% were treated with epinephrine. An underneath IgE-mediated mechanism was proven in all cases. Immunologic cross-reactivity with other TNs was identified in 84%, and with peanut in 36%. Overall, in our center, TNs-FIA represents 18% of all causes of FIA. Conclusions. In preschool age children with TNs-FIA, cashew and walnut were the commonest implicated nuts. Most reactions occurred briefly after exposure to minimal amounts of TNs, demonstrating the high potency of these allergens. About one-third also had peanut sensitization. Potentially life-threatening TNs allergy can occur early in childhood and adequate management should be undertaken.

Peanut allergy and oral immunotherapy.

Peanut allergy is the commonest cause of food-induced anaphylaxis in the world, and it can be fatal. There have been many recent improvements to achieve safe methods of peanut desensitisation, one of which is to use a combination of anti-immunoglobulin E and oral immunotherapy. We have treated 27 patients with anti-immunoglobulin E and oral immunotherapy, and report on the outcomes and incidence of adverse reactions encountered during treatment. The dose of peanut protein tolerated increased from a median baseline of 5 to 2000 mg after desensitisation, which is substantially more than would be encountered through accidental ingestion. The incidence of adverse reactions during the escalation phase of oral immunotherapy was 1.8%, and that during the maintenance phase was 0.6%. Most adverse reactions were mild; three episodes were severe enough to warrant withdrawal from oral immunotherapy, but none required epinephrine injection. Preliminary data suggest that unresponsiveness is lost when daily ingestion of peanuts is stopped after the maintenance period.

Anaphylaxis caused by lipid transfer proteins: an unpredictable clinical syndrome

IntroductionLipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA). ObjectivesDescribe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP. Materials and MethodsForty-three patients were included, aged 3–52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC®). ResultsMedian age of first anaphylactic episode was 24 years (range 2–51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA. ConclusionsLTPs are important allergens of FIA in Portugal. Clinical reactivity to several taxonomically unrelated plant foods may raise suspicion toward LTP sensitization. The association of LTP-induced anaphylaxis with pollinosis is relevant in our country. The unpredictable clinical expression depends on the effect of cofactors such as exercise. The management of avoidance plans can be challenging due to LTP being a widely cross-reacting allergen in plant foods.

Food-induced anaphylaxis in infants and children

BackgroundRecent recommendations to introduce peanut products to infants for peanut allergy prevention requires a focused assessment of infant anaphylaxis. ObjectiveThis study describes the symptomatology of food-induced anaphylaxis (FIA) in infants (<12 months) compared with older pediatric cohorts. MethodsRetrospective review between June 2015 and June 2017 of children presenting with FIA at a large urban children's hospital emergency department (ED). ResultsA total of 357 cases of FIA were evaluated: 47 in infants (<12 months), 43 in toddlers (12-24 months), 96 in young children (2-6 years), and 171 in school-aged children (>6 years). Infants presented with gastrointestinal (GI) involvement more frequently than any other age group (89% vs 63% [P = .003], 60% [P < .001], and 58% [P < .001]). Additionally, infants and young children presented with skin involvement more frequently than school-aged children (94% and 91% vs 62% [P < .001]). Respiratory symptoms were more common in older cohorts (17% in infants vs 44% in young children [P < .001] and 54% in school-aged children [P < .001]). Egg and cow's milk were more common causes of FIA in infants compared with school-aged children (egg, 38% vs 1% [P < .001]; milk, 17% vs 7% [P = .03]). Only 21% of infants with FIA had eczema, and 36% had a history of food allergy. ConclusionInfants with FIA primarily presented with GI and skin manifestations. Egg was the most common food trigger in infants. Most infants with FIA did not have eczema or a history of food allergy.

Effect of thermal processing on T cell reactivity of shellfish allergens - Discordance with IgE reactivity.

Crustacean allergy is a major cause of food-induced anaphylaxis. We showed previously that heating increases IgE reactivity of crustacean allergens. Here we investigate the effects of thermal processing of crustacean extracts on cellular immune reactivity. Raw and cooked black tiger prawn, banana prawn, mud crab and blue swimmer crab extracts were prepared and IgE reactivity assessed by ELISA. Mass spectrometry revealed a mix of several allergens in the raw mud crab extract but predominant heat-stable tropomyosin in the cooked extract. PBMC from crustacean-allergic and non-atopic control subjects were cultured with the crab and prawn extracts and proliferation of lymphocyte subsets was analysed by CFSE labelling and flow cytometry. Effector responses were assessed by intracellular IL-4 and IFN-γ, and regulatory T (CD4+CD25+CD127loFoxp3+) cell proportions in cultures were also compared by flow cytometry. For each crustacean species, the cooked extract had greater IgE reactivity than the raw (mud crab p<0.05, other species p<0.01). In contrast, there was a trend for lower PBMC proliferative responses to cooked compared with raw extracts. In crustacean-stimulated PBMC cultures, dividing CD4+ and CD56+ lymphocytes showed higher IL-4+/IFN-γ+ ratios for crustacean-allergic subjects than for non-atopics (p<0.01), but there was no significant difference between raw and cooked extracts. The percentage IL-4+ of dividing CD4+ cells correlated with total and allergen-specific IgE levels (prawns p<0.01, crabs p<0.05). Regulatory T cell proportions were lower in cultures stimulated with cooked compared with raw extracts (mud crab p<0.001, banana prawn p<0.05). In conclusion, cooking did not substantially alter overall T cell proliferative or cytokine reactivity of crustacean extracts, but decreased induction of Tregs. In contrast, IgE reactivity of cooked extracts was increased markedly. These novel findings have important implications for improved diagnostics, managing crustacean allergy and development of future therapeutics. Assessment of individual allergen T cell reactivity is required.

Age-Based Causes and Clinical Characteristics of Immediate-Type Food Allergy in Korean Children.

PurposeAge-based causes and clinical characteristics of immediate-type food allergy (FA) have not been sufficiently studied. Therefore, we investigated age-dependent clinical profiles of FA in Korean children through an extensive multicenter investigation.MethodsUsing a case report form developed by the authors, a retrospective medical record review was performed of patients (0-18 years old) diagnosed with immediate-type FA between September 2014 and August 2015 in 14 tertiary hospitals in Korea.ResultsA total of 1,353 children and adolescents, 93% younger than 7 years, were enrolled in the present study, and 1,661 cases of immediate-type FA were recorded in these patients. The 7 major causative foods were cow's milk (28.1%), hen's eggs (27.6%), wheat (7.9%), walnuts (7.3%), peanuts (5.3%), buckwheat (1.9%), and shrimps (1.9%). Categorizing the patients into 4 age groups revealed that the most common causative food was different for each age group: cow's milk (<2 years), walnuts (2–6 years), walnuts (7–12 years), and buckwheat (13-18 years). The onset time of symptoms was less than 10 minutes in 49%, between 10 and 30 minutes in 17%, and between 30 minutes and 2 hours in 34% of cases. Food-induced anaphylaxis was reported in 506 (30.5%) out of 1,661 cases, and the 7 major causes of food-induced anaphylaxis was cow's milk (27.5%), hen's eggs (21.9%), wheat (11.3%), walnuts (10.5%), peanuts (5.9%), buckwheat (4.2%), and pine nuts (3.0%). The proportion of anaphylaxis was highest in the patients allergic to buckwheat (67.7%), followed by those allergic to pine nuts (57.7%), walnuts (43.8%), wheat (43.5%), and peanuts (34.1%).ConclusionsThe 5 major causative foods of immediate-type FA in Korean children were cow's milk, hen's eggs, wheat, walnuts, and peanuts. The distribution of causative foods was considerably distinctive according to different age groups. Anaphylaxis was reported in 30.5% of immediate-type FA cases.

An unusual cause of food-induced anaphylaxis in mothers

Background Galacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region.Case presentations We describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions.Conclusions The supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.

Allergenicity attributes of different peanut market types

Four different market classes of peanut (Runner, Virginia Spanish, and Valencia) are commonly consumed in Western countries, but for some consumers peanuts are a main cause of food-induced anaphylaxis. Limited information is available on the comparative allergenicity of these distinct market classes. The aim of this study was to compare allergenicity attributes of different peanut cultivars.The protein content and protein profiles were highly comparable for all tested cultivars. All cultivar samples contained the major allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6, as assessed by SDS-PAGE and RP-HPLC, although some minor differences in major allergen content were found between samples. All samples were reactive in commercial ELISAs for detection and quantification of peanut protein. IgE-binding potency differed between samples with a maximum factor of 2, indicating a highly comparable allergenicity.Based on our observations, we conclude that peanuts from the main market types consumed in Western countries are highly comparable in their allergenicity attributes, indicating that safety considerations with regard to peanut allergy are not dependent on the peanut cultivar in question.

IgE- and T-lymphocyte-Dependent Hypersensitivity Responses Induced in Mice by Exposure to Shrimp (Fenneropenaeus chinensis) Proteins

Shellfish allergy is a common cause of food-induced anaphylaxis in the human, and shrimp is one of the most frequently reported causes of allergic reactions. To identify the immunoglobulin E (IgE)-binding proteins of Chinese shrimp (Fenneropenaeus chinensis), the crude extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS–PAGE) and Western blotting. After exposure of shrimp extracts to mice, the levels of shrimp allergen-specific IgE were determined by indirect ELISA. Histological and immunohistochemical staining of intestinal tract were further performed for immunological analysis. IgE-binding components with molecular masses of 40, 37, 28, 22, and 20 kDa at a high frequency are supposed to be major allergens of F. chinensis. In vivo experiments showed that shrimp extracts could lead to allergen-specific IgE reactivity, and increase mast cell degranulation and numbers of T lymphocytes. IgE- and T-lymphocyte-dependent hypersensitivity plays important roles in allergic reactions triggered by F. chinensis allergens.

Prevalence of Immediate-Type Food Allergy in Early Childhood in Seoul

PurposeThere are scanty epidemiologic data on the prevalence of food allergy (FA) among preschool children in Asia. We performed this study to determine the prevalence and causative foods of immediate-type FA in early childhood in Korea.MethodsA questionnaire-based, cross-sectional study was performed between September and October 2011. Children aged 0-6 years were recruited from 301 public child care centers in Seoul. Parents were asked to complete a questionnaire on FA. Children with FA were classified into "perceived FA, ever," "immediate-type FA, ever," and "immediate-type FA, current" according to the algorithm.ResultsA total of 16,749 children were included in this study. The prevalence of "perceived FA, ever," "immediate-type FA, ever," and "immediate-type FA, current" was 15.1%, 7.0%, and 3.7%, respectively. "Immediate-type FA, current" was reported by 182 (4.9%) out of 3,738 children aged ≤2 years, 262 (3.4%) of 7,648 children aged 3-4 years, and 177 (3.3%) of 5,363 children aged 5-6 years. Hen's egg (126/621) was the most frequent cause as the individual food item, followed by cow's milk (82/621) and peanut (58/621). Among the food groups, fruits (114/621), tree nuts (90/621) and crustaceans (85/621) were the most common offending foods. The three leading causes of food-induced anaphylaxis were hen's egg (22/47), cow's milk (15/47), and peanut (14/47).ConclusionsThe prevalence of immediate-type FA in early childhood is 3.7%, and is higher in younger children. The most common offending foods differed with age.

Allergic Reaction to Peanuts: Can We Predict Reaction Severity in the Wild?

Peanut allergy (PNA) is the main cause of food-induced anaphylaxis. Severe allergic reactions are more likely to occur in older patients and those with underlying asthma. Skin prick testing and measuring serum-specific IgE and recombinant peanut protein levels have been shown to be useful in the diagnosis of PNA and prediction of reactivity, but these tests are less consistent and reliable in terms of predicting the severity of reactions. Recent research has examined the role of biological mediators in allergic reactions such as platelet-activating factor. These may provide a future tool in predicting those at risk of severe reactions. Currently, there are no parameters that can predict with certainty those at risk of anaphylaxis, and management of PNA should continue to focus on patient and family education.

IgE Reactivity of Blue Swimmer Crab (Portunus pelagicus) Tropomyosin, Por p 1, and Other Allergens; Cross-Reactivity with Black Tiger Prawn and Effects of Heating

Shellfish allergy is a major cause of food-induced anaphylaxis, but the allergens are not well characterized. This study examined the effects of heating on blue swimmer crab (Portunus pelagicus) allergens in comparison with those of black tiger prawn (Penaeus monodon) by testing reactivity with shellfish-allergic subjects' serum IgE. Cooked extracts of both species showed markedly increased IgE reactivity by ELISA and immunoblotting, and clinical relevance of IgE reactivity was confirmed by basophil activation tests. Inhibition IgE ELISA and immunoblotting demonstrated cross-reactivity between the crab and prawn extracts, predominantly due to tropomyosin, but crab-specific IgE-reactivity was also observed. The major blue swimmer crab allergen tropomyosin, Por p 1, was cloned and sequenced, showing strong homology with tropomyosin of other crustacean species but also sequence variation within known and predicted linear IgE epitopes. These findings will advance more reliable diagnosis and management of potentially severe food allergy due to crustaceans.

Risk factors for severe pediatric food anaphylaxis in Italy

Little is known about the cause of food-induced anaphylaxis in children or about the factors that might affect its clinical severity. The aim of this study was to investigate the cause of food-induced anaphylaxis in children in Italy and to identify factors that could influence the appearance of symptoms and the severity of anaphylaxis. One hundred and sixty-three children with anaphylaxis consecutively attending 29 outpatient allergy clinics throughout Italy were enrolled in this prospective study. Information about past anaphylaxis episodes was collected with a standardized questionnaire. Food sensitization was evaluated by skin-prick test. A clinical history of asthma increased the risk of wheezing [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5] and respiratory arrest (OR 6.9; 95% CI 1.4-34.2). A clinical history of chronic/relapsing gastrointestinal symptoms increased the risk of vomiting (OR 2.1; 95% CI 0.9-4.3), hypotension (OR 7.9; 95% CI 1.9-32.0), and bradycardia/cardiac arrest (OR 9.2; 95% CI 0.9-91.3). The severity of present and previous episodes was similar only in patients with mild or moderate anaphylaxis. Peanut and egg were the most frequent causes of severe anaphylaxis. A clinical history of asthma and chronic/relapsing gastrointestinal symptoms (probably linked to food allergy) may predict the development of respiratory and gastrointestinal symptoms and the severity of anaphylaxis.

Release of Soluble Protein from Peanut (Arachis hypogaea, Leguminosae) and Its Adsorption by Activated Charcoal

Peanut (Arachis hypogaea, Leguminosae) allergy is a major cause of food-induced anaphylaxis. The potential use of activated charcoal (AC) to adsorb and reduce the bioavailability of peanut protein allergens for use in the moderation of hypersensitivity reactions was investigated. The rate and extent of protein release from peanut and the adsorption of the solubilized protein by AC was determined under physiological pH values and confirmed in vivo using a porcine animal model system. Peanut proteins were adsorbed with equal efficiency at pH 2 and 7 and are completely removed from solution by an AC/protein ratio of approximately 80:1. This suggests that AC can bind protein under gastric (pH 2) or intestinal (pH 7) conditions. The rapid adsorption of soluble peanut allergens and the continuous binding of allergens released from peanut particulate material suggest the potential efficacy of using AC for gastric decontamination and possible elimination of a biphasic allergic reaction.