My immediate goal is to acquire skills necessary for an independent career in patient-oriented research. I need training in design and conduct of patient-oriented research as well in immunology laboratory techniques. My long-term objectives are to stablish myself as an investigator in the field of novel therapies for food allergy. I am confident that at Mount Sinai I am in the nurturing environment committed to my success. I will receive highest-quality mentoring from Dr. Hugh A. Sampson and will have strong support from the Food Allergy Laboratory with access to the state-of-the-art equipment. Clinical Research Training Program to develop solid skills in responsible conduct, design, and analysis of clinical research. Egg allergy is one of the most common food allergies in children. Allergic reactions are more frequently caused by egg white than by egg yolk proteins and ovomucoid is the dominant allergen. Previous studies have demonstrated that children with persistent egg allergy have significantly higher concentrations of IgE-anti-ovomucoid antibodies than those who develop tolerance to egg and those with high IgE-binding activity to pepsin-treated ovomucoid are unlikely to outgrow egg white allergy. We propose to test the following hypotheses: 1.
Specific Aim # 1: Test the hypothesis that egg-allergic children who can ingest extensively heated (baked) egg proteins without experiencing allergic symptoms lack IgE antibodies to sequential egg epitopes compared with children that react to extensively heated egg and possess IgE antibodies to sequential egg epitopes. Children with egg allergy will be challenged to baked products containing cooked egg proteins. Challenge outcome will be compared to epitope recognition. Children tolerating egg in baked goods will be randomized to receive egg-free or egg containing diet, and monitored for 48 months. Egg protein- and epitope- specific IgE and IgG antibodies, intestinal permeability, and growth will be monitored. 2.
Specific Aim # 2: Test the hypothesis that children with more diverse egg IgE epitope recognition patterns have functional consequences on effector cells resulting in more severe reactions and more persistent egg allergy. IgE and IgG antibody avidity and epitope specificity to the two major egg white allergens (ovomucoid and ovalbumin) will be monitored on a yearly basis by peptide array in 90 patients with IgE-mediated egg allergy over 48 months and will be correlated with clinical reactivity to egg determined by double-blinded placebo controlled egg challenges. Antibody avidity will be assessed with thiocyanate disruption. The effector function of IgE antibodies will be assessed by basophil release test with the use of passively sensitized FceRI-transfected rat basophil leukemia cell line stimulated with native and heat-inactivated egg proteins. 3.
Specific Aim# 3: Test the hypothesis that egg-specific IgE antibodies facilitate uptake of egg allergen in the gastrointestinal tract and that the concentration of fecal egg-lgE antibody correlates with intestinal permeability and clinical reactivity to egg in children with egg allergy. We postulate that egg-allergic children have anti-egg IgE antibodies detectable in stool, and that luminal anti-egg IgE antibodies facilitate the uptake of egg allergen, resulting in clinical symptoms and increased intestinal permeability. Stool samples will be obtained prior to and following each oral egg challenge (at multiple time points over 48 months) in children participating in a clinical trial described in Aim # 1. Total and egg-specific IgE, egg-lgE and egg-specific IgG will be determined in each stool sample and correlated with clinical outcome of the oral egg challenge. Intestinal permeability will be tested prior to baseline egg challenges in all children participating in Aim # 1 and following oral egg challenges in a smaller subset of patients. Intestinal permeability will also be measured at 3 and 12 months, and correlated with oral egg challenge outcome, fecal and serum anti-egg IgE and anti-egg IgG antibody levels.
|Konstantinou, George N; Nowak-W?grzyn, Anna; Bencharitiwong, Ramon et al. (2014) Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: is there a role in tolerance induction? Pediatr Allergy Immunol 25:64-70|
|Järvinen, Kirsi M; Konstantinou, George N; Pilapil, Mariecel et al. (2013) Intestinal permeability in children with food allergy on specific elimination diets. Pediatr Allergy Immunol 24:589-95|
|Leonard, Stephanie A; Sampson, Hugh A; Sicherer, Scott H et al. (2012) Dietary baked egg accelerates resolution of egg allergy in children. J Allergy Clin Immunol 130:473-80.e1|
|Caubet, Jean Christoph; Bencharitiwong, Ramon; Moshier, Erin et al. (2012) Significance of ovomucoid- and ovalbumin-specific IgE/IgG(4) ratios in egg allergy. J Allergy Clin Immunol 129:739-47|
|Järvinen, Kirsi M; Caubet, Jean-Christoph; Sickles, Laura et al. (2012) Poor utility of atopy patch test in predicting tolerance development in food protein-induced enterocolitis syndrome. Ann Allergy Asthma Immunol 109:221-2|
|Maloney, Jennifer M; Nowak-W?grzyn, Anna; Wang, Julie (2011) Children in the inner city of New York have high rates of food allergy and IgE sensitization to common foods. J Allergy Clin Immunol 128:214-5|
|Martos, Gustavo; Lopez-Exposito, Ivan; Bencharitiwong, Ramon et al. (2011) Mechanisms underlying differential food allergy response to heated egg. J Allergy Clin Immunol 127:990-7.e1-2|
|Wang, Julie; Lin, Jing; Bardina, Ludmilla et al. (2010) Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol 125:695-702, 702.e1-702.e6|
|Wanich, Niya; Bencharitiwong, Ramon; Tsai, Theodore et al. (2010) In vitro assessment of the allergenicity of a novel influenza vaccine produced in dog kidney cells in individuals with dog allergy. Ann Allergy Asthma Immunol 104:426-33|
|Jarvinen, Kirsi M; Amalanayagam, Sujitha; Shreffler, Wayne G et al. (2009) Epinephrine treatment is infrequent and biphasic reactions are rare in food-induced reactions during oral food challenges in children. J Allergy Clin Immunol 124:1267-72|
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