Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:To review current evidence on food oral immunotherapy (OIT). RECENT FINDINGS/RESULTS:Desensitized state, defined as the ingestion of a substantial amount of food in the home diet that protects from severe reactions to accidental exposures, can be achieved by approximately 50-75% of the children treated with OIT. The rate of permanent tolerance is unknown; the longer duration of OIT may result in permanent tolerance. Side effects are common both during the initial dose escalation and during home dosing. Most reactions are mild (oral pruritus, abdominal discomfort, and rashes) and decrease in frequency with the longer duration of OIT. Severe reactions treated with epinephrine have been reported during home dosing. Factors associated with increased risk of reactions to previously tolerated doses during home dosing include exercise, viral infection, dosing on empty stomach, menses, and asthma exacerbation. SUMMARY/CONCLUSIONS:These preliminary data on OIT are encouraging. Additional studies must answer multiple questions including optimal dose, ideal duration of oral/sublingual immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment and need for patient protection during home administration. Until these questions are answered in rigorous multicenter randomized and placebo-controlled trials, OIT remains an experimental approach with not sufficiently well established risk-to-benefit ratio.

BACKGROUND:An inactivated influenza vaccine produced in canine kidney cells (MDCK 33016-PF) contains no egg proteins and may be used to immunize egg-allergic patients. Although no major dog allergens were identified in MDCK 33016-PF cells, minor dog allergens might be present and cause reactions in dog-allergic individuals. OBJECTIVE:To evaluate the allergenicity of the inactivated influenza vaccine produced in cell culture in a mediator release assay. METHODS:Rat basophil leukemia (RBL) cells transfected with human IgE receptor-1 were sensitized with sera from dog-allergic adults with positive skin prick test reactions to dog extract and detectable dog dander IgE and were stimulated with serial dilutions of vaccine and dog dander extract. N-hexosaminidase release (NHR) was used as a marker of RBL cell degranulation. Western blots were performed, and UniCAP was used to measure dog-specific IgE antibody levels. RESULTS:The median (interquartile range) level of dog dander IgE was 8.31 kU(A)/L (1.895-14.5 kU(A)/L) and of dog epithelium IgE was 3.19 kU(A)/L (0.835-6.27 kU(A)L). Median (range) maximum NHR (at the first 10-fold dilution) was 0% (0%-1.4%) to vaccine and 10.2% (0%-35.9%) to dog dander (P < .001). In an egg-allergic control subject, the maximum NHR to a vaccine cultured in chick embryo and containing egg protein was 10.2%. IgE antibodies in pooled sera did not bind to vaccine on immunoblots but produced strong binding to dog dander and epithelium extracts. Serum from an egg-allergic control subject strongly bound embryonated egg-derived vaccine. CONCLUSION/CONCLUSIONS:An influenza vaccine produced in continuous canine kidney cells did not trigger degranulation in RBL cells passively sensitized with human anti-dog IgE.

Egg allergy is one of the most frequent food allergies in children below the age of three. Common symptoms of egg allergy involve frequently the skin as well as the gut and in more severe cases result in anaphylaxis. Non-IgE-mediated symptoms such as in eosinophilic diseases of the gut or egg-induced enterocolitis might also be observed. Sensitization to egg white proteins can be found in young children in absence of clinical symptoms. The diagnosis of egg allergy is based on the history, IgE tests as well as standardized food challenges. Ovomucoid is the major allergen of egg, and recent advances in technology have improved the diagnosis and follow-up of patients with egg allergy by using single allergens or allergens with modified allergenic properties. Today, the management of egg allergy is strict avoidance. However, oral tolerance induction protocols, in particular with egg proteins with reduced allergenic properties, are promising tools for inducing an increased level of tolerance in specific patients.

BACKGROUND:Results from large-scale epitope mapping with a peptide microarray have been shown to correlate with clinical features of milk allergy. OBJECTIVES/OBJECTIVE:We sought to assess IgE and IgG4 epitope diversity and IgE affinity in different clinical phenotypes of milk allergy and identify informative epitopes that might be predictive of clinical outcomes of milk allergy. METHODS:Forty-one subjects were recruited from a larger study on the effects of ingesting heat-denatured milk proteins in subjects with milk allergy. Using food challenges, subjects were characterized as being clinically reactive to all forms of milk (n = 17), being tolerant to heated milk (HM) products (n = 16), or having outgrown their milk allergy (n = 8). Eleven healthy volunteers without milk allergy served as control subjects. A peptide microarray was performed by using the previously published protocol. RESULTS:Subjects with milk allergy had increased epitope diversity compared with those who outgrew their allergy. HM-tolerant subjects had IgE-binding patterns similar to those who had outgrown their allergy, but IgG4-binding patterns that were more similar to those of the allergic group. Binding to higher numbers of IgE peptides was associated with more severe allergic reactions during challenge. There was no association between IgG4 peptides and clinical features of milk allergy. Using a competitive peptide microarray assay, allergic patients demonstrated a combination of high- and low-affinity IgE binding, whereas HM-tolerant subjects and those who had outgrown their milk allergy had primarily low-affinity binding. CONCLUSIONS:Greater IgE epitope diversity and higher affinity, as determined by using the peptide microarray, were associated with clinical phenotypes and severity of milk allergy.

BACKGROUND:Data about epinephrine use and biphasic reactions in childhood food-induced anaphylaxis during oral food challenges are scarce. OBJECTIVE:To determine the prevalence and risk factors of reactions requiring epinephrine and the rate of biphasic reactions during oral food challenges (OFCs) in children. METHODS:Reaction details of positive OFCs in children between 1999 and 2007 were collected by using a computerized database. Selection of patients for OFCs was generally predicated on < or =50% likelihood of a positive challenge and a low likelihood of a severe reaction on the basis of the clinical history, specific IgE levels, and skin prick tests. RESULTS:A total of 436 of 1273 OFCs resulted in a reaction (34%). Epinephrine was administered in 50 challenges (11% of positive challenges, 3.9% overall) for egg (n = 15, 16% of positive OFCs to egg), milk (n = 14, 12%), peanut (n = 10, 26%), tree nuts (n = 4, 33%), soy (n = 3, 7%), wheat (n = 3, 9%), and fish (n = 1, 9%). Reactions requiring epinephrine occurred in older children (median, 7.9 vs 5.8 years; P < .001) and were more often caused by peanuts (P = .006) compared with reactions not treated with epinephrine. There was no difference in the sex, prevalence of asthma, history of anaphylaxis, specific IgE level, skin prick tests, or amount of food administered. Two doses of epinephrine were required in 3 of 50 patients (6%) reacting to wheat, cow's milk, and pistachio. There was 1 (2%) biphasic reaction. No reaction resulted in life-threatening respiratory or cardiovascular compromise. CONCLUSION/CONCLUSIONS:Older age and reactions to peanuts were risk factors for anaphylaxis during oral food challenges. Reactions requiring multiple doses of epinephrine and biphasic reactions were infrequent.

PURPOSE OF REVIEW/OBJECTIVE:To review current knowledge and recent advances in food protein-induced enterocolitis syndrome (FPIES). RECENT FINDINGS/RESULTS:Rice is the most common solid food causing FPIES. Rice FPIES is associated with more severe reactions than other foods. Infants presenting acutely may be hypothermic (<36 degrees C) and have thrombocytosis. Finding of hypoalbuminemia and weight gain less than 10 g/day helps to differentiate chronic infantile cow's milk FPIES from infectious causes. Gastric juice leukocytes more than 10 cells per high-power field are found in infants with positive oral food challenge to cow's milk. SUMMARY/CONCLUSIONS:FPIES is a non-IgE-mediated gastrointestinal food hypersensitivity disorder. Food protein-activated intestinal lymphocytes elaborate inflammatory cytokines that result in increased intestinal permeability, malabsorption, dysmotility, emesis, diarrhea, pain, and failure to thrive. Decreased intestinal transforming growth factor beta and increased TNFalpha may be important in FPIES. Cow's milk and soy are the most common causes of FPIES, but cereal grains (rice, oat, and barley), fish, poultry, and vegetables may also cause FPIES. The majority of FPIES resolve by age of 3 years.

BACKGROUND:Shellfish allergy is a long-lasting disorder usually persisting throughout life. Despite its high prevalence, there is limited information about allergenic shrimp proteins. OBJECTIVE:Characterization of shrimp allergens. METHODS:Fifty-two adults and children with a history of immediate allergic reactions to shrimp and elevated serum IgE to shrimp were selected for this study. Tryptic digests from a 20-kd IgE-binding protein were analyzed by LC-MS/MS, identifying the protein as a sarcoplasmic-calcium-binding protein. cDNA encoding sarcoplasmic calcium-binding protein (SCP) from a shrimp cDNA library (Litopenaeus vannamei) was amplified by PCR, cloned into an expression vector, and sequenced. Recombinant SCP was tested with patients' sera. ELISA inhibition experiments determined the fraction of total shrimp IgE recognizing SCP. A functional assay with a rat basophilic leukemia cell line was used to determine the capacity for mediator release induced by SCP. RESULTS:Immunoblotting demonstrated IgE binding by 31 of 52 (59.6%) of the sera to a 20-kd shrimp protein. The protein was identified as a SCP. Amplified cDNA encoding SCP was isolated and sequenced. Open reading frame translation provided the complete amino acid sequence of shrimp SCP. Recombinant SCP was recognized by serum IgE from 20 of 52 (38.4%) subjects, of whom 17 of 20 (85%) were children. ELISA inhibition of pooled sera IgE reactivity to BS extract using recombinant SCP was significant (as high as 79%). For some subjects, mediator release induced by recombinant SCP was higher than that induced by recombinant tropomyosin. CONCLUSION/CONCLUSIONS:We have identified and cloned a new shrimp allergen, Lit v 4.0101, an SCP, which appears to be of particular importance in the pediatric population.