Summary and recommendations: Classification of gastrointestinal manifestations due to immunologic reactions to foods in infants and young children.
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Food Hypersensitivity↗
Biomedical subjects
H A Sampson
Publications and source records attributed to H A Sampson.
Peanut and tree nut allergy.
Among foods causing allergic reactions in children, peanut (a legume) and tree nuts (ie, walnut, hazel nut, Brazil nut, pecan) have attracted considerable attention for several reasons. Allergies to these foods are common, frequently have an onset in the first few years of life, generally persist, and account for severe and potentially fatal allergic reactions. Furthermore, the ubiquity of these foods in the diet makes avoidance difficult and accidental ingestions, with reactions, common. This review discusses recent and emerging information on the prevalence, clinical characteristics, natural history, genetic basis, and current treatment of these allergies. In addition, recent advances in the molecular and immunologic characteristics of these allergens, and novel therapeutic options under investigation in animal models, are reviewed.
Arachis↗
Definitive diagnosis of nut allergy.
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Food Hypersensitivity↗
A soybean G2 glycinin allergen. 1. Identification and characterization.
BACKGROUND: Multiple allergens have been documented in soybean extracts. IgE from individuals allergic to soybeans, but not to peanut, was shown by immunoblot analysis to bind to proteins with a molecular weight of approximately 21 kD. These findings suggested that unique proteins in soybeans might be responsible for soybean allergic reactivity. The objective of the present study was to identify unique proteins in soybean extracts that bind to specific IgE from soybean-sensitive individuals, and to characterize the allergen using physicochemical methods and IgE binding. METHODS: Two-dimensional and preparative SDS-PAGE/IgE immunoblot analysis was used to identify a 22-kD soybean-specific allergen from crude soybean extracts. N-terminal sequence analysis was used to determine the identification of the protein binding IgE from soybean-sensitive individuals. RESULTS: IgE immunoblot and amino acid sequence analysis identified the 22-kD protein as a member of the G2 glycinin soybean protein family. Further investigation revealed that the IgEs reacted with basic chains from each member of the glycinin family of soybean storage proteins. CONCLUSIONS: Each of the subunits from glycinin, the storage protein that is the most prevalent component of soybean, are major allergens.
Allergens↗
A soybean G2 glycinin allergen. 2. Epitope mapping and three-dimensional modeling.
BACKGROUND: Multiple allergens have been documented in soybean extracts. IgE from individuals allergic to soybeans, but not to peanut, has been shown by immunoblot analysis to bind to proteins with a molecular weight of approximately 22 kD. These findings suggested that this unique protein fraction from soybean might be responsible, in part, for soybean allergic reactivity. The objective of the present study was to characterize specific B cell epitopes, to determine if any amino acid was critical to IgE binding and to model the 22-kD G2 soybean allergen to the three-dimensional (3-D) phaseolin molecule. METHODS: B cell epitopes were identified using SPOTs peptide analysis. Structural orientation of the IgE-binding regions was mapped to the 3-D phaseolin molecule using molecular modeling of the protein tertiary structure. RESULTS: Eleven linear epitopes, representing 15 amino acid peptide sequences, bound to IgE in the glycinin molecule. These epitopes were predicted to be distributed asymmetrically on the surface of G2 trimers. CONCLUSIONS: Only 1 epitope could be rendered non-IgE binding by alanine substitutions in the peptide. The nonrandom distribution of the IgE binding sites provides new insight into their organization in trimers in 11S complexes of the G2 glycinin allergen.
Alanine↗
Food anaphylaxis.
Food anaphylaxis is now the leading single cause of anaphylactic reactions treated in emergency departments in Westernized countries. In the US, it is estimated that there are 29,000 anaphylactic reactions to foods treated in emergency departments and 125-150 deaths each year. Peanuts, tree nuts, fish and shellfish account for the vast majority of severe food anaphylactic reactions. Immunopathogenic mechanisms responsible for food anaphylaxis may differ somewhat from other forms of anaphylaxis, since elevation of serum tryptase is rarely seen following food anaphylactic reactions. Education regarding the strict avoidance of food allergens, the early recognition of anaphylactic symptoms, and the early use of self-injectable epinephrine remain the mainstays of therapy. However, clinical trials are now underway for the treatment of patients with peanut anaphylaxis utilizing anti-IgE antibody therapy and novel immunomodulatory therapies utilizing 'engineered' recombinant proteins, overlapping peptides, and immunostimulatory deoxyoligonucleotide sequences are being tested in animal models of anaphylaxis.
Acute Disease↗
Comparison of molecular and conventional strategies for followup of superficial bladder cancer using decision analysis.
PURPOSE: Patients with superficial bladder cancer require long-term surveillance for recurrence. We compared the cost of cystoscopy and cytology (standard care) to that of urinary markers (modified care) for patients with a history of superficial bladder cancer. MATERIALS AND METHODS: We constructed a decision analysis model that compared the 2 strategies for a hypothetical followup interval of 3 years. Probabilities required for the decision tree were based on a cohort of 361 patients diagnosed with superficial bladder cancer from 1987 to 1997. Sensitivity analyses were used to determine whether test sensitivity and specificity would affect cost thresholds. Costs for each strategy were then applied to actual practice patterns. RESULTS: The cost of modified care ranged from $158 to $228 for each followup visit when using a urinary marker with a sensitivity and specificity of 95% and 77%, respectively. The cost of standard care was $240 for each followup visit. Based on sensitivity analyses the probability of disease recurrence and urinary marker accuracy were important determinants of expected costs. Mean number of followup assessments for patients followed more than 3 years was 4.3, 2.2 and 1.5 for years 1, 2 and 3, respectively. Cumulative costs of modified care were lower than those of standard care. CONCLUSIONS: Urinary marker testing for followup of patients with superficial bladder cancer is less expensive than the standard method of cystoscopy and urinary cytology based on our model. Future studies will be required to consider other factors that could affect the cost advantage of urinary markers, including indirect costs, the psychosocial impact of testing and different surveillance frequencies.
Decision Support Techniques↗
Strain-dependent induction of allergic sensitization caused by peanut allergen DNA immunization in mice.
To investigate the potential application of allergen gene immunization in the modulation of food allergy, C3H/HeSn (C3H) mice received i.m. injections of pAra h2 plasmid DNA encoding one of the major peanut allergens, Ara h2. Three weeks following pDNA immunization, serum Ara h2-specific IgG2a, IgG1, but not IgE, were increased significantly in a dose-dependent manner. IgG1 was 30-fold higher in multiply compared with singly immunized mice. Ara h2 or peanut protein injection of immunized mice induced anaphylactic reactions, which were more severe in multiply immunized mice. Heat-inactivated immune serum induced passive cutaneous anaphylaxis, suggesting that anaphylaxis in C3H mice was mediated by IgG1. IgG1 responses were also induced by intradermal injection of pAra h2, and by i.m. injection of pOMC, the plasmid DNA encoding the major egg allergen protein, ovomucoid. To elucidate whether the pDNA immunization-induced anaphylaxis was a strain-dependent phenomenon, AKR/J and BALB/c mice also received multiple i.m. pAra h2 immunizations. Injection of peanut protein into these strains at weeks 3 or 5 following immunization did not induce reactions. Although IgG2a was increased significantly from week 2 in AKR/J mice and from week 4 in BALB/c mice and remained elevated for at least 6 wk, no IgG1 or IgE was detected. These results indicate that the type of immune responses to pDNA immunization in mice is strain dependent. Consequently, models for studying human allergen gene immunization require careful selection of suitable strains. In addition, this suggests that similar interindividual variation is likely in humans.
Allergens↗
Anaphylaxis and food allergy.
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Anaphylaxis↗
Soy allergy in infants and children with IgE-associated cow's milk allergy.
OBJECTIVES: To determine the prevalence of soy allergy in IgE-associated cow's milk allergy (CMA). STUDY DESIGN: Children <3.5 years with documented IgE-associated CMA (n = 93) were evaluated for soy allergy by double-blind, placebo-controlled food challenge, open challenge, or convincing previous history of an anaphylactic reaction to soy. Children tolerant to soy at entry received soy formula and were followed up for 1 year. RESULTS: Of this IgE-associated CMA cohort (ages 3 to 41 months), 14% (95% CI = 7. 7%-22.7%) were determined to have soy allergy, 12 definitely at entry and 1 possibly after 1 year of soy ingestion. The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion. Improved growth (P <.05) occurred in the non-soy-allergic cohort ingesting soy formula (579 31 mL/d) during the year of follow-up. CONCLUSIONS: Soy allergy occurs in only a small minority of young children with IgE-associated CMA. As such, soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula.
Child, Preschool↗
Food hypersensitivity and atopic dermatitis: pathophysiology, epidemiology, diagnosis, and management.
Laboratory and clinical investigations over the past two decades have demonstrated that food allergy plays a pathogenic role in a subset of patients, primarily infants and children, with atopic dermatitis (AD). Approximately 40% of infants and young children with moderate to severe AD have food allergy, but identifying this subset of patients and isolating the relevant food allergens requires a high index of suspicion, the use of appropriate laboratory tests, and, in some cases, physician-supervised oral food challenges. Removal of the causal food protein(s) leads to clinical improvement but requires a great deal of education because most of the common causal foods (egg, milk, wheat, soy, peanut, and so forth) are ubiquitous in the food supply, and food elimination diets risk causing nutritional deficits. Fortunately, most food allergies resolve in early childhood, and food allergy is not a common cause for AD in older children and adults.
Adult↗
Adult-onset sensitization to casein after occupational exposure to aerosolized Tryptone powder.
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Adult↗
Self-reported allergic reactions to peanut on commercial airliners.
BACKGROUND: Allergic reactions to food occurring on commercial airlines have not been systematically characterized. OBJECTIVE: We sought to describe the clinical characteristics of allergic reactions to peanuts on airplanes. METHODS: Participants in the National Registry of Peanut and Tree Nut Allergy who indicated an allergic reaction while on a commercial airliner were interviewed by telephone. RESULTS: Sixty-two of 3704 National Registry of Peanut and Tree Nut Allergy participants indicated a reaction on an airplane; 42 of 48 patients or parental surrogates contacted confirmed the reaction began on the airplane (median age of affected subject, 2 years; range, 6 months to 50 years). Of these, 35 reacted to peanuts (4 were uncertain of exposure) and 7 to tree nuts, although 3 of these 7 reacted to substances that may have also contained peanut. Exposures occurred by ingestion (20 subjects), skin contact (8 subjects), and inhalation (14 subjects). Reactions generally occurred within 10 minutes of exposure (32 of 42 subjects), and reaction severity correlated with exposure route (ingestion > inhalation > skin). The causal food was generally served by the airline (37 of 42 subjects). Medications were given in flight to 19 patients (epinephrine to 5) and to an additional 14 at landing/gate return (including epinephrine to 1 and intravenous medication to 2), totaling 79% treated. Flight crews were notified in 33% of reactions. During inhalation reactions as a result of peanut allergy, greater than 25 passengers were estimated to be eating peanuts at the time of the reaction. Initial symptoms generally involved the upper airway, with progression to the skin or further lower respiratory reactions (no gastrointestinal symptoms). CONCLUSIONS: Allergic reactions to peanuts and tree nuts caused by accidental ingestion, skin contact, or inhalation occur during commercial flights, but airline personnel are usually not notified. Reactions can be severe, requiring medications, including epinephrine.
Aerospace Medicine↗
Food allergy. Part 2: diagnosis and management.
Patients with food-induced allergic disorders may be first seen with a variety of symptoms affecting the skin, respiratory tract, gastrointestinal tract, and/or cardiovascular system. The skin and respiratory tract are most often affected by IgE-mediated food-induced allergic reactions, whereas isolated gastrointestinal disorders are most often caused by non-IgE-mediated reactions. When evaluating possible food-induced allergic disorders, it is often useful to categorize disorders into IgE- and non-IgE-mediated syndromes. The initial history and physical examination are essentially identical for IgE- and non-IgE-mediated disorders, but the subsequent evaluation differs substantially. Proper diagnoses often require screening tests for evidence of food-specific IgE and proof of reactivity through elimination diets and oral food challenges. Once properly diagnosed, strict avoidance of the implicated food or foods is the only proven form of treatment. Clinical tolerance to food allergens will develop in many patients over time, and therefore follow-up food challenges are often indicated. However, a number of novel immunomodulatory strategies are in the developmental stage and should provide more definitive treatment for some of these food-induced allergic disorders in the next several years.
Double-Blind Method↗
Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey.
BACKGROUND: Allergy to peanuts and tree nuts (TNs) is one of the leading causes of fatal and near-fatal food-induced allergic reactions. These allergies can be lifelong and appear to be increasing in prevalence. Despite the seriousness of these allergies, the prevalence of peanut and TN allergy in the general population is unknown. OBJECTIVE: We sought to determine the prevalence of peanut and TN allergy among the general population of the United States. METHODS: We used a nationwide, cross-sectional, random digit dial telephone survey with a standardized questionnaire. RESULTS: A total of 4374 households contacted by telephone participated (participation rate, 67%), representing 12,032 individuals. Peanut or TN allergy was self-reported in 164 individuals (1.4%; 95% confidence interval [CI], 1.2%-1.6%) in 151 households (3.5%; 95% CI, 2.9%-4.0%). The prevalence of reported allergy in adults (1.6%) was higher than that found in children under 18 years of age (0.6%). In 131 individuals, details of the reactions were obtained. When applying criteria requiring reactions to be typical of IgE-mediated reactions (hives, angioedema, wheezing, throat tightness, vomiting, and diarrhea) within an hour of ingestion, 10% of these subjects were excluded. Among the remaining 118 subjects, allergic reactions involved 1 organ system (skin, respiratory, or gastrointestinal systems) in 50 subjects, 2 in 45 subjects, and all 3 in 23 subjects. Forty-five percent of these 118 respondents reported more than 5 lifetime reactions. Only 53% of these 118 subjects ever saw a physician for the allergic reaction, and only 7% had self-injectable epinephrine available at the time of the interview. The prevalence of peanut and TN allergy was adjusted by assuming that 10% of the remaining 33 subjects without a description of their reactions would also be excluded and correcting for a 7% false-positive rate for the survey instrument. A final "corrected" prevalence estimate of 1.1% (95% CI, 1.0%-1.4%) was obtained. CONCLUSIONS: Peanut and/or TN allergy affects approximately 1.1% of the general population, or about 3 million Americans, representing a significant health concern. Despite the severity of reactions, about half of the subjects never sought an evaluation by a physician, and only a few had epinephrine available for emergency use.
Adolescent↗
Food allergy. Part 1: immunopathogenesis and clinical disorders.
Up to 8% of children less than 3 years of age and approximately 2% of the adult population experience food-induced allergic disorders. A limited number of foods are responsible for the vast majority of food-induced allergic reactions: milk, egg, peanuts, fish, and tree nuts in children and peanuts, tree nuts, fish, and shellfish in adults. Food-induced allergic reactions are responsible for a variety of symptoms involving the skin, gastrointestinal tract, and respiratory tract and may be caused by IgE-mediated and non-IgE-mediated mechanisms. In part 1 of this series, immunopathogenic mechanisms and clinical disorders of food allergy are described.
Food Hypersensitivity↗
A murine model of IgE-mediated cow's milk hypersensitivity.
BACKGROUND: Cow's milk allergy (CMA) is one of the leading causes of food allergy in children. Understanding the mechanisms involved in the development of CMA has been hampered by the lack of suitable animal models. OBJECTIVE: We sought to develop a mouse model of IgE-mediated cow's milk hypersensitivity (CMH) that mimics the clinical features of immediate CMA in humans. METHODS: Three-week-old C3H/HeJ mice were sensitized by intragastric administration of cow's milk (CM) plus cholera toxin and boosted 5 times at weekly intervals. RESULTS: CM-specific IgE antibody levels were significantly increased at 3 weeks and peaked at 6 weeks after the initial feeding. Intragastric challenge with CM at week 6 elicited systemic anaphylaxis accompanied by vascular leakage, significantly increased plasma histamine, and increased intestinal permeability to casein. Histologic examination of intestinal tissue revealed marked vascular congestion, edema, and sloughing of enterocytes. The role of IgE in mediating CMH was confirmed by abrogation of passive cutaneous anaphylaxis reactions by heat inactivation of immune sera. Development of IgE-mediated CMH in this model is likely to be TH2 cell mediated because in vitro stimulation of spleen cells from mice allergic to CM induced significant increases in the levels of IL-4 and IL-5, but not IFN-gamma. CONCLUSION: This model should provide a useful tool for evaluating the immunopathogenic mechanisms involved in CMA and for exploring new therapeutic approaches.
Adjuvants, Immunologic↗
Cow's milk protein-specific IgE concentrations in two age groups of milk-allergic children and in children achieving clinical tolerance.
BACKGROUND: IgE-mediated cow's milk protein allergy (CMPA) is usually outgrown in children by the age of 3 years. The immunological responses to cow's milk proteins in children who achieve tolerance, in comparison with those who remain allergic, however, are not well described. OBJECTIVE: To compare the level of cow's milk protein-specific IgE among children with documented CMPA under the age of 3 years, another group over the age of 9 years (persistent allergy), and in another group of children in whom clinical tolerance developed. METHODS: Stored sera from children with CMPA were analysed for IgE antibodies specific for whole cow's milk, casein, whey, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), and bovine serum albumin (BSA) using the Pharmacia CAP System FEIA. RESULTS: Within each group of CMPA children, the concentration of specific IgE antibody to casein proteins was not significantly different from that to whey proteins. However, children in the group with CMPA over 9 years of age had significantly greater concentrations of whole milk (P = 0.02) and casein-specific (P = 0. 04) IgE antibodies compared with the group of children with CMPA under age 3 years. Children under the age of 3 years had a higher median concentration of casein-specific IgE (20.2 vs. 5.5, P = 0.04) than another group of 11 children (mean age 3.5 years), who later lost their milk allergy. Out of 16 children who lost sensitivity to milk, 75% had milk-specific IgE levels below 14.3 kUA/L (median, 1.3 kUA/L). CONCLUSIONS: Although a dominant allergenic milk protein fraction was not identified within either of the two age groups, those with persistent CMPA over age 9 years had significantly elevated levels of milk and casein-specific IgE compared with younger children with CMPA.
Adolescent↗