E•A•T is solely focused on funding research. We do not fund other food allergy related initiatives such as educational programming, publications, advocacy related efforts, operations for treatment centers, etc. While these are extremely important initiatives, we believe other organizations do them very well.
Goal is to accelerate research
Our goal is to accelerate the most promising ideas in food allergy research toward the clinical testing and expansion of shorter-term treatments and longer term solutions involved in the root causes, triggers, and processes of food allergy progression.
Objective funding process
Our medical advisory board is comprised of highly knowledgeable scientists and physicians who are leaders in the field but not conducting their own studies.
EAT has funded the following studies:
Biomarkers
1 ‘Molecular Gene Expression During Allergic Reactions to Food: Identifying Signatures Which Correlate with Severity of Reaction’
Jonathan M. Spergel, MD, PhD, Division of Allergy-Immunology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania
Paul J. Turner, FRACP PhD, Section of Pediatrics (Allergy-Immunology), Faculty of Medicine, Imperial College London, United Kingdom.
2 ‘Developing Non-Invasive Biomarkers for Eosinophilic Esophagitis by Molecular Profiling of the Buccal Mucosa’
Marc E. Rothenberg, MD, PhD, Director, Division of Allergy and Immunology; Director, Cincinnati Center for Eosinophilic Disorders, Cincinnati Children’s Hospital Medical Center
Leah Kottyan, PhD, Assistant Professor, Department of Pediatrics, University of Cincinnati College of Medicine Center for Autoimmune Genomics and Etiology (CAGE) , Cincinnati Children’s Hospital Medical Center
Microbiome
‘Characterization of Prebiotic Dietary Fibers to Prevent or Treat Food Allergy’
Cathryn R. Nagler, PhD, Bunning Food Allergy Professor, Professor of Pathology, Medicine, Pediatrics and The College, The University of Chicago
Oral Immunotherapy
‘Improving Safety for the Food Allergy-Asthma Syndrome’
Sharon Chinthrajah, MD, Kari Nadeau, MD, PhD, Pulmonary and Critical Care Medicine, Allergy and Immunology, Sean N Parker Center for Allergy and Asthma Research, Stanford University
Eosinophilic Esophagitis
‘Use of Esophageal String Test to understand symptoms, inflammation and function in eosinophilic esophagitis.’
Glenn Furuta, MD, Director, Gastrointestinal Eosinophilic Disease Program Le Cache Endowed Chair for GI Allergic and Immunologic Diseases, Children’s Hospital Colorado
Jonathan M. Spergel, MD, PhD, Division of Allergy-Immunology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania
‘Molecular Gene Expression During Allergic Reactions to Food: Identifying Signatures Which Correlate with Severity of Reaction’
Jonathan M. Spergel, MD, PhD, Division of Allergy-Immunology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania
Paul J. Turner, FRACP PhD, Section of Pediatrics (Allergy-Immunology), Faculty of Medicine, Imperial College London, United Kingdom.
The biggest challenge in managing individuals with food allergy is our current inability to reliably identify those people who are at risk of severe, life-threatening reaction. Our knowledge regarding the mechanisms of food allergic reactions in man is limited, partly due to the fact that animal models are of very limited relevance. We cannot explain why one person will develop life-threatening anaphylaxis to under 1/70 of a peanut, while another will develop only localized itching after eating 3-4 peanuts. Allergy tests (skin prick test size, specific IgE antibody to either a total allergen or allergen component) do not predict the severity or the sensitivity of an individual. For example, a patient with small skin test can have life-threatening allergic reaction, while another patient with a large skin test may have a mild reaction limited to the skin.
Understanding the mechanisms, and in particular the differences between severe and non-severe allergic reactions, is key to improving patient care. In this research we will take advantage of blood samples from a unique cohort of peanut-allergic patients that have undergone carefully-controlled food challenges to peanut under varying conditions and experienced different types of reactions.
We will use advanced molecular techniques (microarray gene expression CHIP assay) to study expression of genes which are activated during allergic reactions and then result in the release of mediators which cause the reaction. We will analyze these results to identify how the different gene expression signals are associated with the symptoms experienced by patients. The goal is to identify molecular signatures that correlate with patterns of symptoms allowing us to predict who is at risk for a severe reaction.
‘Developing Non-Invasive Biomarkers for Eosinophilic Esophagitis by Molecular Profiling of the Buccal Mucosa’
Marc E. Rothenberg, MD, PhD, Director, Division of Allergy and Immunology; Director, Cincinnati Center for Eosinophilic Disorders, Cincinnati Children’s Hospital Medical Center
Leah Kottyan, PhD, Assistant Professor, Department of Pediatrics, University of Cincinnati College of Medicine Center for Autoimmune Genomics and Etiology (CAGE) , Cincinnati Children’s Hospital Medical Center
Eosinophilic esophagitis (EoE) is an emerging allergic disease characterized by chronic, food-induced,esophagus-specific inflammation associated with high levels of tissue eosinophils in the esophagus (1). The disease often presents in early life as failure to thrive, abdominal pain and/or vomiting and is followed by dysphagia and food impactions in adolescents and adults (2). Though EoE is chronic and persists from childhood into adulthood, the disease is reversible following treatment with dietary elimination and/or topical glucocorticoid therapy (3). Diagnosis of EoE is currently dependent upon endoscopic evaluation followed by esophageal biopsy, as threshold levels of esophageal eosinophils are required for diagnosis (>15 peak eosinophils/high-powered field [HPF]). In addition to EoE being associated with often debilitating symptoms, restricted diets, and reduced quality of life, patients with EoE often have to undergo repeat endoscopies, as there are no other ways to determine disease activity, including the presence of remission, as symptoms do not often correlate with tissue pathology and there are currently no useful non-invasive biomarkers that can be used to monitor the disease (4). The need for repetitive endoscopies is costly in terms of financial burden, time (e.g., missed days from school and work), and risk, as pediatric anesthesia been associated with cognitive decline (5). Thus, the purpose of this study is to develop improved indicators (biomarkers) for EoE diagnosis and assessment through a non-invasive test for diagnosis and monitoring based on molecular sampling of oral (buccal) samples.
‘Characterization of Prebiotic Dietary Fibers to Prevent or Treat Food Allergy’
Cathryn R. Nagler, PhD, Bunning Food Allergy Professor, Professor of Pathology, Medicine, Pediatrics and The College, The University of Chicago
Immunoregulatory responses induced by commensal bacteria are critical to preventing intestinal inflammation. Whether the intestinal microbiota also plays a role in regulating non responsiveness to the other major luminal constituent – food – has been poorly understood. Murine models developed in our laboratory demonstrate that sensitization to a food allergen is enhanced in mice that have been treated by neonatal antibiotic administration (Abx) or are devoid of commensal microbes (germ free). By selectively colonizing germ free mice we showed that the allergy-protective capacity is contained within the Clostridia, a class of anaerobic spore forming Firmicutes that resides in close proximity to the intestinal epithelium. Reintroduction of a Clostridia-containing microbiota to Abx-treated mice blocks sensitization to a food allergen. Microarray analysis of intestinal epithelial cells isolated from gnotobiotic mice identified a novel innate mechanism by which Clostridia protect against sensitization to dietary antigens. Clostridia colonization induces the production of the barrier protective cytokine IL-22 by both innate lymphoid cells and T cells in the intestinal lamina propria. IL-22-mediated effector functions, including the production of mucus and anti-microbial peptides, collectively contribute to protection against sensitization by reducing the access of dietary antigen to the systemic circulation. Our mouse model work is supported by translational studies comparing the fecal microbiota of healthy infants to that of infants with cow’s milk allergy (CMA). We find that the CMA infant microbiome has the diverse community structure typical of adults. Treatment of CMA infants with a tolerance inducing formula supplemented with the probiotic Lactobacillus rhamnosus GG (LGG) is associated with changes in microbial community structure that include the expansion of butyrate-producing Clostridia and significantly higher levels of butyrate detectable in feces. Butyrate, but not other short chain fatty acids, regulates epithelial barrier function in our mouse model. Commensal bacteria produce butyrate by fermentation of insoluble dietary fiber and we also find that mice weaned onto high fiber diets exhibit reduced intestinal permeability to food antigens. Identification of dietary fibers, and their metabolites, which regulate the intestinal epithelial barrier has great promise for the development of novel microbiome modulating approaches to prevent or treat allergic sensitization to food.
‘Improving Safety for the Food Allergy-Asthma Syndrome’
Sharon Chinthrajah, MD, Kari Nadeau, MD, PhD, Pulmonary and Critical Care Medicine, Allergy and Immunology, Sean N Parker Center for Allergy and Asthma Research, Stanford University
Oral immunotherapy (OIT) is an emerging investigational therapy for food allergy. With multiple small exploratory trials and some large randomized-controlled phase 2 trials recently published, there is clear progress and interest toward making this a treatment option for patients suffering from food allergies. Understanding who is at risk for more severe reactions during OIT, the immunological mechanisms underlying the increased risk, and how to make OIT a safer process would help to make this therapy more widely available.
In patients with food allergy, asthma is a risk factor for a life threatening reaction.1,2 Interestingly, both diseases have overlapping immune mechanisms leading to “allergic inflammation” characterized by eosinophils, allergic antibodies, such as IgE, and T helper cells (Th2 cells). Though T cells are understood to be central mediators of both asthma and food allergy separately, little is known about the contribution of different T cell subsets to a combined food allergy-asthma syndrome. Recently, we have shown that omalizumab, an anti-IgE antibody extensively studied in asthma, can also be used in conjunction with OIT to desensitize patients to their food allergies in a safe and expedient manner, compared to OIT alone.4
We will to understand distinct food allergic phenotypes and determine the relative contributions of T cell subsets in these different groups and how this contributes to the safety of OIT in patients undergoing OIT with and without Omalizumab. Results from these studies will improve our understanding of the interaction between food allergy and asthma, and lead to the understanding of how omalizumab may increase safety and symptoms of these diseases during oral immunotherapy.
‘Use of Esophageal String Test to understand symptoms, inflammation and function in eosinophilic esophagitis.’
Glenn Furuta, MD, Director, Gastrointestinal Eosinophilic Disease Program Le Cache Endowed Chair for GI Allergic and Immunologic Diseases, Children’s Hospital Colorado
Jonathan M. Spergel, MD, PhD, Division of Allergy-Immunology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania
Procurement of mucosal biopsies during sedated endoscopy is the only method to determine whether a child may have eosinophilic esophagitis (EoE). Counting esophageal eosinophils in the squamous epithelium remains key to establishing the diagnosis. To date, no blood, stool, breath or other peripheral sampling of eosinophil related biomarkers has been shown to correlate with mucosal eosinophilia in esophageal biopsies, thus leaving patients and families with the
only option of undergoing this invasive, costly and time consuming procedure.
Sedated upper endoscopy with biopsy is a safe procedure, but alternative methods that do not encumber exposure to anesthetic agents and address other problematic features are needed to obtain diagnostic samples. Although eosinophils are easy to count, variability exists with respect to reporting and better biomarkers must be determined. In this regard, we, and others showed that effluents obtained from the esophageal lumen are reflective of esophageal eosinophilia. Katzka et al determined that the esophageal sponge is able to harvest mucosal scrapings to measure eosinophils (10). This approach is not suitable for children because of its size and tolerability. Our work documents that the Esophageal String Test (EST) can detect luminal biomarkers that reflect esophageal eosinophilic infiltration (2). This capsule based technology is well tolerated by children ages 7 years and up, and fluid adherent to the string has been shown to contain eosinophil granule proteins that correlate with esophageal eosinophilia and amounts of these proteins in biopsies.
The overall goal of this study is to discover a less invasive fashion to make the EoE diagnosis and assess disease activity in children. Here, we will determine whether eosinophil granule proteins captured by the EST correlate with: a) EoE symptoms, b) EoE histopathological scores and c) a new functional biometric.
Interested grant applicants should please contact us at [email protected]